DNA mismatch repair proteins MLH1 and PMS2 can be imported to the nucleus by a classical nuclear import pathway
MLH1 and PMS2 proteins form the MutLα heterodimer, which plays a major role in DNA mismatch repair (MMR) in humans. Mutations in MMR-related proteins are associated with cancer, especially with colon cancer. The N-terminal region of MutLα comprises the N-termini of PMS2 and MLH1 and, similarly, the...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
de Barros, Andrea C. [verfasserIn] |
|---|
| Format: |
E-Artikel |
|---|---|
| Sprache: |
Englisch |
| Erschienen: |
2018transfer abstract |
|---|
| Schlagwörter: |
Nuclear localization sequence (NLS) |
|---|
| Umfang: |
10 |
|---|
| Übergeordnetes Werk: |
Enthalten in: Energy-saving improvement of heat integration for separating dilute azeotropic components in extractive distillation - Duan, Cong ELSEVIER, 2022, an international journal of biochemistry and molecular biology, Paris [u.a.] |
|---|---|
| Übergeordnetes Werk: |
volume:146 ; year:2018 ; pages:87-96 ; extent:10 |
| Links: |
|---|
| DOI / URN: |
10.1016/j.biochi.2017.11.013 |
|---|
| Katalog-ID: |
ELV041896556 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | ELV041896556 | ||
| 003 | DE-627 | ||
| 005 | 20230625235943.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 180726s2018 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.biochi.2017.11.013 |2 doi | |
| 028 | 5 | 2 | |a GBV00000000000506.pica |
| 035 | |a (DE-627)ELV041896556 | ||
| 035 | |a (ELSEVIER)S0300-9084(17)30308-5 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 082 | 0 | 4 | |a 600 |q VZ |
| 084 | |a 50.70 |2 bkl | ||
| 100 | 1 | |a de Barros, Andrea C. |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a DNA mismatch repair proteins MLH1 and PMS2 can be imported to the nucleus by a classical nuclear import pathway |
| 264 | 1 | |c 2018transfer abstract | |
| 300 | |a 10 | ||
| 336 | |a nicht spezifiziert |b zzz |2 rdacontent | ||
| 337 | |a nicht spezifiziert |b z |2 rdamedia | ||
| 338 | |a nicht spezifiziert |b zu |2 rdacarrier | ||
| 520 | |a MLH1 and PMS2 proteins form the MutLα heterodimer, which plays a major role in DNA mismatch repair (MMR) in humans. Mutations in MMR-related proteins are associated with cancer, especially with colon cancer. The N-terminal region of MutLα comprises the N-termini of PMS2 and MLH1 and, similarly, the C-terminal region of MutLα is composed by the C-termini of PMS2 and MLH1, and the two are connected by linker region. The nuclear localization sequences (NLSs) necessary for the nuclear transport of the two proteins are found in this linker region. However, the exact NLS sequences have been controversial, with different sequences reported, particularly for MLH1. The individual components are not imported efficiently, presumably due to their C-termini masking their NLSs. In order to gain insights into the nuclear transport of these proteins, we solved the crystal structures of importin-α bound to peptides corresponding to the supposed NLSs of MLH1 and PMS2 and performed isothermal titration calorimetry to study their binding affinities. Both putative MLH1 and PMS2 NLSs can bind to importin-α as monopartite NLSs, which is in agreement with some previous studies. However, MLH1-NLS has the highest affinity measured by a natural NLS peptide, suggesting a major role of MLH1 protein in nuclear import compared to PMS2. Finally, the role of MLH1 and PMS2 in the nuclear transport of the MutLα heterodimer is discussed. | ||
| 520 | |a MLH1 and PMS2 proteins form the MutLα heterodimer, which plays a major role in DNA mismatch repair (MMR) in humans. Mutations in MMR-related proteins are associated with cancer, especially with colon cancer. The N-terminal region of MutLα comprises the N-termini of PMS2 and MLH1 and, similarly, the C-terminal region of MutLα is composed by the C-termini of PMS2 and MLH1, and the two are connected by linker region. The nuclear localization sequences (NLSs) necessary for the nuclear transport of the two proteins are found in this linker region. However, the exact NLS sequences have been controversial, with different sequences reported, particularly for MLH1. The individual components are not imported efficiently, presumably due to their C-termini masking their NLSs. In order to gain insights into the nuclear transport of these proteins, we solved the crystal structures of importin-α bound to peptides corresponding to the supposed NLSs of MLH1 and PMS2 and performed isothermal titration calorimetry to study their binding affinities. Both putative MLH1 and PMS2 NLSs can bind to importin-α as monopartite NLSs, which is in agreement with some previous studies. However, MLH1-NLS has the highest affinity measured by a natural NLS peptide, suggesting a major role of MLH1 protein in nuclear import compared to PMS2. Finally, the role of MLH1 and PMS2 in the nuclear transport of the MutLα heterodimer is discussed. | ||
| 650 | 7 | |a X-ray crystallography |2 Elsevier | |
| 650 | 7 | |a Nuclear localization sequence (NLS) |2 Elsevier | |
| 650 | 7 | |a Importin-α |2 Elsevier | |
| 650 | 7 | |a Nuclear import pathway |2 Elsevier | |
| 650 | 7 | |a MLH1 and PMS2 proteins |2 Elsevier | |
| 650 | 7 | |a Isothermal titration calorimetry |2 Elsevier | |
| 650 | 7 | |a DNA repair |2 Elsevier | |
| 700 | 1 | |a Takeda, Agnes A.S. |4 oth | |
| 700 | 1 | |a Dreyer, Thiago R. |4 oth | |
| 700 | 1 | |a Velazquez-Campoy, Adrian |4 oth | |
| 700 | 1 | |a Kobe, Boštjan |4 oth | |
| 700 | 1 | |a Fontes, Marcos R.M. |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |n Elsevier |a Duan, Cong ELSEVIER |t Energy-saving improvement of heat integration for separating dilute azeotropic components in extractive distillation |d 2022 |d an international journal of biochemistry and molecular biology |g Paris [u.a.] |w (DE-627)ELV008857954 |
| 773 | 1 | 8 | |g volume:146 |g year:2018 |g pages:87-96 |g extent:10 |
| 856 | 4 | 0 | |u https://doi.org/10.1016/j.biochi.2017.11.013 |3 Volltext |
| 912 | |a GBV_USEFLAG_U | ||
| 912 | |a GBV_ELV | ||
| 912 | |a SYSFLAG_U | ||
| 936 | b | k | |a 50.70 |j Energie: Allgemeines |q VZ |
| 951 | |a AR | ||
| 952 | |d 146 |j 2018 |h 87-96 |g 10 | ||
| author_variant |
b a c d bac bacd |
|---|---|
| matchkey_str |
debarrosandreactakedaagnesasdreyerthiago:2018----:nmsacrpipoenmhadm2abipretteulubals |
| hierarchy_sort_str |
2018transfer abstract |
| bklnumber |
50.70 |
| publishDate |
2018 |
| allfields |
10.1016/j.biochi.2017.11.013 doi GBV00000000000506.pica (DE-627)ELV041896556 (ELSEVIER)S0300-9084(17)30308-5 DE-627 ger DE-627 rakwb eng 600 VZ 50.70 bkl de Barros, Andrea C. verfasserin aut DNA mismatch repair proteins MLH1 and PMS2 can be imported to the nucleus by a classical nuclear import pathway 2018transfer abstract 10 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier MLH1 and PMS2 proteins form the MutLα heterodimer, which plays a major role in DNA mismatch repair (MMR) in humans. Mutations in MMR-related proteins are associated with cancer, especially with colon cancer. The N-terminal region of MutLα comprises the N-termini of PMS2 and MLH1 and, similarly, the C-terminal region of MutLα is composed by the C-termini of PMS2 and MLH1, and the two are connected by linker region. The nuclear localization sequences (NLSs) necessary for the nuclear transport of the two proteins are found in this linker region. However, the exact NLS sequences have been controversial, with different sequences reported, particularly for MLH1. The individual components are not imported efficiently, presumably due to their C-termini masking their NLSs. In order to gain insights into the nuclear transport of these proteins, we solved the crystal structures of importin-α bound to peptides corresponding to the supposed NLSs of MLH1 and PMS2 and performed isothermal titration calorimetry to study their binding affinities. Both putative MLH1 and PMS2 NLSs can bind to importin-α as monopartite NLSs, which is in agreement with some previous studies. However, MLH1-NLS has the highest affinity measured by a natural NLS peptide, suggesting a major role of MLH1 protein in nuclear import compared to PMS2. Finally, the role of MLH1 and PMS2 in the nuclear transport of the MutLα heterodimer is discussed. MLH1 and PMS2 proteins form the MutLα heterodimer, which plays a major role in DNA mismatch repair (MMR) in humans. Mutations in MMR-related proteins are associated with cancer, especially with colon cancer. The N-terminal region of MutLα comprises the N-termini of PMS2 and MLH1 and, similarly, the C-terminal region of MutLα is composed by the C-termini of PMS2 and MLH1, and the two are connected by linker region. The nuclear localization sequences (NLSs) necessary for the nuclear transport of the two proteins are found in this linker region. However, the exact NLS sequences have been controversial, with different sequences reported, particularly for MLH1. The individual components are not imported efficiently, presumably due to their C-termini masking their NLSs. In order to gain insights into the nuclear transport of these proteins, we solved the crystal structures of importin-α bound to peptides corresponding to the supposed NLSs of MLH1 and PMS2 and performed isothermal titration calorimetry to study their binding affinities. Both putative MLH1 and PMS2 NLSs can bind to importin-α as monopartite NLSs, which is in agreement with some previous studies. However, MLH1-NLS has the highest affinity measured by a natural NLS peptide, suggesting a major role of MLH1 protein in nuclear import compared to PMS2. Finally, the role of MLH1 and PMS2 in the nuclear transport of the MutLα heterodimer is discussed. X-ray crystallography Elsevier Nuclear localization sequence (NLS) Elsevier Importin-α Elsevier Nuclear import pathway Elsevier MLH1 and PMS2 proteins Elsevier Isothermal titration calorimetry Elsevier DNA repair Elsevier Takeda, Agnes A.S. oth Dreyer, Thiago R. oth Velazquez-Campoy, Adrian oth Kobe, Boštjan oth Fontes, Marcos R.M. oth Enthalten in Elsevier Duan, Cong ELSEVIER Energy-saving improvement of heat integration for separating dilute azeotropic components in extractive distillation 2022 an international journal of biochemistry and molecular biology Paris [u.a.] (DE-627)ELV008857954 volume:146 year:2018 pages:87-96 extent:10 https://doi.org/10.1016/j.biochi.2017.11.013 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 50.70 Energie: Allgemeines VZ AR 146 2018 87-96 10 |
| spelling |
10.1016/j.biochi.2017.11.013 doi GBV00000000000506.pica (DE-627)ELV041896556 (ELSEVIER)S0300-9084(17)30308-5 DE-627 ger DE-627 rakwb eng 600 VZ 50.70 bkl de Barros, Andrea C. verfasserin aut DNA mismatch repair proteins MLH1 and PMS2 can be imported to the nucleus by a classical nuclear import pathway 2018transfer abstract 10 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier MLH1 and PMS2 proteins form the MutLα heterodimer, which plays a major role in DNA mismatch repair (MMR) in humans. Mutations in MMR-related proteins are associated with cancer, especially with colon cancer. The N-terminal region of MutLα comprises the N-termini of PMS2 and MLH1 and, similarly, the C-terminal region of MutLα is composed by the C-termini of PMS2 and MLH1, and the two are connected by linker region. The nuclear localization sequences (NLSs) necessary for the nuclear transport of the two proteins are found in this linker region. However, the exact NLS sequences have been controversial, with different sequences reported, particularly for MLH1. The individual components are not imported efficiently, presumably due to their C-termini masking their NLSs. In order to gain insights into the nuclear transport of these proteins, we solved the crystal structures of importin-α bound to peptides corresponding to the supposed NLSs of MLH1 and PMS2 and performed isothermal titration calorimetry to study their binding affinities. Both putative MLH1 and PMS2 NLSs can bind to importin-α as monopartite NLSs, which is in agreement with some previous studies. However, MLH1-NLS has the highest affinity measured by a natural NLS peptide, suggesting a major role of MLH1 protein in nuclear import compared to PMS2. Finally, the role of MLH1 and PMS2 in the nuclear transport of the MutLα heterodimer is discussed. MLH1 and PMS2 proteins form the MutLα heterodimer, which plays a major role in DNA mismatch repair (MMR) in humans. Mutations in MMR-related proteins are associated with cancer, especially with colon cancer. The N-terminal region of MutLα comprises the N-termini of PMS2 and MLH1 and, similarly, the C-terminal region of MutLα is composed by the C-termini of PMS2 and MLH1, and the two are connected by linker region. The nuclear localization sequences (NLSs) necessary for the nuclear transport of the two proteins are found in this linker region. However, the exact NLS sequences have been controversial, with different sequences reported, particularly for MLH1. The individual components are not imported efficiently, presumably due to their C-termini masking their NLSs. In order to gain insights into the nuclear transport of these proteins, we solved the crystal structures of importin-α bound to peptides corresponding to the supposed NLSs of MLH1 and PMS2 and performed isothermal titration calorimetry to study their binding affinities. Both putative MLH1 and PMS2 NLSs can bind to importin-α as monopartite NLSs, which is in agreement with some previous studies. However, MLH1-NLS has the highest affinity measured by a natural NLS peptide, suggesting a major role of MLH1 protein in nuclear import compared to PMS2. Finally, the role of MLH1 and PMS2 in the nuclear transport of the MutLα heterodimer is discussed. X-ray crystallography Elsevier Nuclear localization sequence (NLS) Elsevier Importin-α Elsevier Nuclear import pathway Elsevier MLH1 and PMS2 proteins Elsevier Isothermal titration calorimetry Elsevier DNA repair Elsevier Takeda, Agnes A.S. oth Dreyer, Thiago R. oth Velazquez-Campoy, Adrian oth Kobe, Boštjan oth Fontes, Marcos R.M. oth Enthalten in Elsevier Duan, Cong ELSEVIER Energy-saving improvement of heat integration for separating dilute azeotropic components in extractive distillation 2022 an international journal of biochemistry and molecular biology Paris [u.a.] (DE-627)ELV008857954 volume:146 year:2018 pages:87-96 extent:10 https://doi.org/10.1016/j.biochi.2017.11.013 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 50.70 Energie: Allgemeines VZ AR 146 2018 87-96 10 |
| allfields_unstemmed |
10.1016/j.biochi.2017.11.013 doi GBV00000000000506.pica (DE-627)ELV041896556 (ELSEVIER)S0300-9084(17)30308-5 DE-627 ger DE-627 rakwb eng 600 VZ 50.70 bkl de Barros, Andrea C. verfasserin aut DNA mismatch repair proteins MLH1 and PMS2 can be imported to the nucleus by a classical nuclear import pathway 2018transfer abstract 10 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier MLH1 and PMS2 proteins form the MutLα heterodimer, which plays a major role in DNA mismatch repair (MMR) in humans. Mutations in MMR-related proteins are associated with cancer, especially with colon cancer. The N-terminal region of MutLα comprises the N-termini of PMS2 and MLH1 and, similarly, the C-terminal region of MutLα is composed by the C-termini of PMS2 and MLH1, and the two are connected by linker region. The nuclear localization sequences (NLSs) necessary for the nuclear transport of the two proteins are found in this linker region. However, the exact NLS sequences have been controversial, with different sequences reported, particularly for MLH1. The individual components are not imported efficiently, presumably due to their C-termini masking their NLSs. In order to gain insights into the nuclear transport of these proteins, we solved the crystal structures of importin-α bound to peptides corresponding to the supposed NLSs of MLH1 and PMS2 and performed isothermal titration calorimetry to study their binding affinities. Both putative MLH1 and PMS2 NLSs can bind to importin-α as monopartite NLSs, which is in agreement with some previous studies. However, MLH1-NLS has the highest affinity measured by a natural NLS peptide, suggesting a major role of MLH1 protein in nuclear import compared to PMS2. Finally, the role of MLH1 and PMS2 in the nuclear transport of the MutLα heterodimer is discussed. MLH1 and PMS2 proteins form the MutLα heterodimer, which plays a major role in DNA mismatch repair (MMR) in humans. Mutations in MMR-related proteins are associated with cancer, especially with colon cancer. The N-terminal region of MutLα comprises the N-termini of PMS2 and MLH1 and, similarly, the C-terminal region of MutLα is composed by the C-termini of PMS2 and MLH1, and the two are connected by linker region. The nuclear localization sequences (NLSs) necessary for the nuclear transport of the two proteins are found in this linker region. However, the exact NLS sequences have been controversial, with different sequences reported, particularly for MLH1. The individual components are not imported efficiently, presumably due to their C-termini masking their NLSs. In order to gain insights into the nuclear transport of these proteins, we solved the crystal structures of importin-α bound to peptides corresponding to the supposed NLSs of MLH1 and PMS2 and performed isothermal titration calorimetry to study their binding affinities. Both putative MLH1 and PMS2 NLSs can bind to importin-α as monopartite NLSs, which is in agreement with some previous studies. However, MLH1-NLS has the highest affinity measured by a natural NLS peptide, suggesting a major role of MLH1 protein in nuclear import compared to PMS2. Finally, the role of MLH1 and PMS2 in the nuclear transport of the MutLα heterodimer is discussed. X-ray crystallography Elsevier Nuclear localization sequence (NLS) Elsevier Importin-α Elsevier Nuclear import pathway Elsevier MLH1 and PMS2 proteins Elsevier Isothermal titration calorimetry Elsevier DNA repair Elsevier Takeda, Agnes A.S. oth Dreyer, Thiago R. oth Velazquez-Campoy, Adrian oth Kobe, Boštjan oth Fontes, Marcos R.M. oth Enthalten in Elsevier Duan, Cong ELSEVIER Energy-saving improvement of heat integration for separating dilute azeotropic components in extractive distillation 2022 an international journal of biochemistry and molecular biology Paris [u.a.] (DE-627)ELV008857954 volume:146 year:2018 pages:87-96 extent:10 https://doi.org/10.1016/j.biochi.2017.11.013 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 50.70 Energie: Allgemeines VZ AR 146 2018 87-96 10 |
| allfieldsGer |
10.1016/j.biochi.2017.11.013 doi GBV00000000000506.pica (DE-627)ELV041896556 (ELSEVIER)S0300-9084(17)30308-5 DE-627 ger DE-627 rakwb eng 600 VZ 50.70 bkl de Barros, Andrea C. verfasserin aut DNA mismatch repair proteins MLH1 and PMS2 can be imported to the nucleus by a classical nuclear import pathway 2018transfer abstract 10 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier MLH1 and PMS2 proteins form the MutLα heterodimer, which plays a major role in DNA mismatch repair (MMR) in humans. Mutations in MMR-related proteins are associated with cancer, especially with colon cancer. The N-terminal region of MutLα comprises the N-termini of PMS2 and MLH1 and, similarly, the C-terminal region of MutLα is composed by the C-termini of PMS2 and MLH1, and the two are connected by linker region. The nuclear localization sequences (NLSs) necessary for the nuclear transport of the two proteins are found in this linker region. However, the exact NLS sequences have been controversial, with different sequences reported, particularly for MLH1. The individual components are not imported efficiently, presumably due to their C-termini masking their NLSs. In order to gain insights into the nuclear transport of these proteins, we solved the crystal structures of importin-α bound to peptides corresponding to the supposed NLSs of MLH1 and PMS2 and performed isothermal titration calorimetry to study their binding affinities. Both putative MLH1 and PMS2 NLSs can bind to importin-α as monopartite NLSs, which is in agreement with some previous studies. However, MLH1-NLS has the highest affinity measured by a natural NLS peptide, suggesting a major role of MLH1 protein in nuclear import compared to PMS2. Finally, the role of MLH1 and PMS2 in the nuclear transport of the MutLα heterodimer is discussed. MLH1 and PMS2 proteins form the MutLα heterodimer, which plays a major role in DNA mismatch repair (MMR) in humans. Mutations in MMR-related proteins are associated with cancer, especially with colon cancer. The N-terminal region of MutLα comprises the N-termini of PMS2 and MLH1 and, similarly, the C-terminal region of MutLα is composed by the C-termini of PMS2 and MLH1, and the two are connected by linker region. The nuclear localization sequences (NLSs) necessary for the nuclear transport of the two proteins are found in this linker region. However, the exact NLS sequences have been controversial, with different sequences reported, particularly for MLH1. The individual components are not imported efficiently, presumably due to their C-termini masking their NLSs. In order to gain insights into the nuclear transport of these proteins, we solved the crystal structures of importin-α bound to peptides corresponding to the supposed NLSs of MLH1 and PMS2 and performed isothermal titration calorimetry to study their binding affinities. Both putative MLH1 and PMS2 NLSs can bind to importin-α as monopartite NLSs, which is in agreement with some previous studies. However, MLH1-NLS has the highest affinity measured by a natural NLS peptide, suggesting a major role of MLH1 protein in nuclear import compared to PMS2. Finally, the role of MLH1 and PMS2 in the nuclear transport of the MutLα heterodimer is discussed. X-ray crystallography Elsevier Nuclear localization sequence (NLS) Elsevier Importin-α Elsevier Nuclear import pathway Elsevier MLH1 and PMS2 proteins Elsevier Isothermal titration calorimetry Elsevier DNA repair Elsevier Takeda, Agnes A.S. oth Dreyer, Thiago R. oth Velazquez-Campoy, Adrian oth Kobe, Boštjan oth Fontes, Marcos R.M. oth Enthalten in Elsevier Duan, Cong ELSEVIER Energy-saving improvement of heat integration for separating dilute azeotropic components in extractive distillation 2022 an international journal of biochemistry and molecular biology Paris [u.a.] (DE-627)ELV008857954 volume:146 year:2018 pages:87-96 extent:10 https://doi.org/10.1016/j.biochi.2017.11.013 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 50.70 Energie: Allgemeines VZ AR 146 2018 87-96 10 |
| allfieldsSound |
10.1016/j.biochi.2017.11.013 doi GBV00000000000506.pica (DE-627)ELV041896556 (ELSEVIER)S0300-9084(17)30308-5 DE-627 ger DE-627 rakwb eng 600 VZ 50.70 bkl de Barros, Andrea C. verfasserin aut DNA mismatch repair proteins MLH1 and PMS2 can be imported to the nucleus by a classical nuclear import pathway 2018transfer abstract 10 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier MLH1 and PMS2 proteins form the MutLα heterodimer, which plays a major role in DNA mismatch repair (MMR) in humans. Mutations in MMR-related proteins are associated with cancer, especially with colon cancer. The N-terminal region of MutLα comprises the N-termini of PMS2 and MLH1 and, similarly, the C-terminal region of MutLα is composed by the C-termini of PMS2 and MLH1, and the two are connected by linker region. The nuclear localization sequences (NLSs) necessary for the nuclear transport of the two proteins are found in this linker region. However, the exact NLS sequences have been controversial, with different sequences reported, particularly for MLH1. The individual components are not imported efficiently, presumably due to their C-termini masking their NLSs. In order to gain insights into the nuclear transport of these proteins, we solved the crystal structures of importin-α bound to peptides corresponding to the supposed NLSs of MLH1 and PMS2 and performed isothermal titration calorimetry to study their binding affinities. Both putative MLH1 and PMS2 NLSs can bind to importin-α as monopartite NLSs, which is in agreement with some previous studies. However, MLH1-NLS has the highest affinity measured by a natural NLS peptide, suggesting a major role of MLH1 protein in nuclear import compared to PMS2. Finally, the role of MLH1 and PMS2 in the nuclear transport of the MutLα heterodimer is discussed. MLH1 and PMS2 proteins form the MutLα heterodimer, which plays a major role in DNA mismatch repair (MMR) in humans. Mutations in MMR-related proteins are associated with cancer, especially with colon cancer. The N-terminal region of MutLα comprises the N-termini of PMS2 and MLH1 and, similarly, the C-terminal region of MutLα is composed by the C-termini of PMS2 and MLH1, and the two are connected by linker region. The nuclear localization sequences (NLSs) necessary for the nuclear transport of the two proteins are found in this linker region. However, the exact NLS sequences have been controversial, with different sequences reported, particularly for MLH1. The individual components are not imported efficiently, presumably due to their C-termini masking their NLSs. In order to gain insights into the nuclear transport of these proteins, we solved the crystal structures of importin-α bound to peptides corresponding to the supposed NLSs of MLH1 and PMS2 and performed isothermal titration calorimetry to study their binding affinities. Both putative MLH1 and PMS2 NLSs can bind to importin-α as monopartite NLSs, which is in agreement with some previous studies. However, MLH1-NLS has the highest affinity measured by a natural NLS peptide, suggesting a major role of MLH1 protein in nuclear import compared to PMS2. Finally, the role of MLH1 and PMS2 in the nuclear transport of the MutLα heterodimer is discussed. X-ray crystallography Elsevier Nuclear localization sequence (NLS) Elsevier Importin-α Elsevier Nuclear import pathway Elsevier MLH1 and PMS2 proteins Elsevier Isothermal titration calorimetry Elsevier DNA repair Elsevier Takeda, Agnes A.S. oth Dreyer, Thiago R. oth Velazquez-Campoy, Adrian oth Kobe, Boštjan oth Fontes, Marcos R.M. oth Enthalten in Elsevier Duan, Cong ELSEVIER Energy-saving improvement of heat integration for separating dilute azeotropic components in extractive distillation 2022 an international journal of biochemistry and molecular biology Paris [u.a.] (DE-627)ELV008857954 volume:146 year:2018 pages:87-96 extent:10 https://doi.org/10.1016/j.biochi.2017.11.013 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 50.70 Energie: Allgemeines VZ AR 146 2018 87-96 10 |
| language |
English |
| source |
Enthalten in Energy-saving improvement of heat integration for separating dilute azeotropic components in extractive distillation Paris [u.a.] volume:146 year:2018 pages:87-96 extent:10 |
| sourceStr |
Enthalten in Energy-saving improvement of heat integration for separating dilute azeotropic components in extractive distillation Paris [u.a.] volume:146 year:2018 pages:87-96 extent:10 |
| format_phy_str_mv |
Article |
| bklname |
Energie: Allgemeines |
| institution |
findex.gbv.de |
| topic_facet |
X-ray crystallography Nuclear localization sequence (NLS) Importin-α Nuclear import pathway MLH1 and PMS2 proteins Isothermal titration calorimetry DNA repair |
| dewey-raw |
600 |
| isfreeaccess_bool |
false |
| container_title |
Energy-saving improvement of heat integration for separating dilute azeotropic components in extractive distillation |
| authorswithroles_txt_mv |
de Barros, Andrea C. @@aut@@ Takeda, Agnes A.S. @@oth@@ Dreyer, Thiago R. @@oth@@ Velazquez-Campoy, Adrian @@oth@@ Kobe, Boštjan @@oth@@ Fontes, Marcos R.M. @@oth@@ |
| publishDateDaySort_date |
2018-01-01T00:00:00Z |
| hierarchy_top_id |
ELV008857954 |
| dewey-sort |
3600 |
| id |
ELV041896556 |
| language_de |
englisch |
| fullrecord |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">ELV041896556</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230625235943.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">180726s2018 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.biochi.2017.11.013</subfield><subfield code="2">doi</subfield></datafield><datafield tag="028" ind1="5" ind2="2"><subfield code="a">GBV00000000000506.pica</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)ELV041896556</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(ELSEVIER)S0300-9084(17)30308-5</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">600</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">50.70</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">de Barros, Andrea C.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">DNA mismatch repair proteins MLH1 and PMS2 can be imported to the nucleus by a classical nuclear import pathway</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2018transfer abstract</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">10</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zzz</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">z</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zu</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">MLH1 and PMS2 proteins form the MutLα heterodimer, which plays a major role in DNA mismatch repair (MMR) in humans. Mutations in MMR-related proteins are associated with cancer, especially with colon cancer. The N-terminal region of MutLα comprises the N-termini of PMS2 and MLH1 and, similarly, the C-terminal region of MutLα is composed by the C-termini of PMS2 and MLH1, and the two are connected by linker region. The nuclear localization sequences (NLSs) necessary for the nuclear transport of the two proteins are found in this linker region. However, the exact NLS sequences have been controversial, with different sequences reported, particularly for MLH1. The individual components are not imported efficiently, presumably due to their C-termini masking their NLSs. In order to gain insights into the nuclear transport of these proteins, we solved the crystal structures of importin-α bound to peptides corresponding to the supposed NLSs of MLH1 and PMS2 and performed isothermal titration calorimetry to study their binding affinities. Both putative MLH1 and PMS2 NLSs can bind to importin-α as monopartite NLSs, which is in agreement with some previous studies. However, MLH1-NLS has the highest affinity measured by a natural NLS peptide, suggesting a major role of MLH1 protein in nuclear import compared to PMS2. Finally, the role of MLH1 and PMS2 in the nuclear transport of the MutLα heterodimer is discussed.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">MLH1 and PMS2 proteins form the MutLα heterodimer, which plays a major role in DNA mismatch repair (MMR) in humans. Mutations in MMR-related proteins are associated with cancer, especially with colon cancer. The N-terminal region of MutLα comprises the N-termini of PMS2 and MLH1 and, similarly, the C-terminal region of MutLα is composed by the C-termini of PMS2 and MLH1, and the two are connected by linker region. The nuclear localization sequences (NLSs) necessary for the nuclear transport of the two proteins are found in this linker region. However, the exact NLS sequences have been controversial, with different sequences reported, particularly for MLH1. The individual components are not imported efficiently, presumably due to their C-termini masking their NLSs. In order to gain insights into the nuclear transport of these proteins, we solved the crystal structures of importin-α bound to peptides corresponding to the supposed NLSs of MLH1 and PMS2 and performed isothermal titration calorimetry to study their binding affinities. Both putative MLH1 and PMS2 NLSs can bind to importin-α as monopartite NLSs, which is in agreement with some previous studies. However, MLH1-NLS has the highest affinity measured by a natural NLS peptide, suggesting a major role of MLH1 protein in nuclear import compared to PMS2. Finally, the role of MLH1 and PMS2 in the nuclear transport of the MutLα heterodimer is discussed.</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">X-ray crystallography</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Nuclear localization sequence (NLS)</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Importin-α</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Nuclear import pathway</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">MLH1 and PMS2 proteins</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Isothermal titration calorimetry</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">DNA repair</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Takeda, Agnes A.S.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Dreyer, Thiago R.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Velazquez-Campoy, Adrian</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Kobe, Boštjan</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Fontes, Marcos R.M.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="n">Elsevier</subfield><subfield code="a">Duan, Cong ELSEVIER</subfield><subfield code="t">Energy-saving improvement of heat integration for separating dilute azeotropic components in extractive distillation</subfield><subfield code="d">2022</subfield><subfield code="d">an international journal of biochemistry and molecular biology</subfield><subfield code="g">Paris [u.a.]</subfield><subfield code="w">(DE-627)ELV008857954</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:146</subfield><subfield code="g">year:2018</subfield><subfield code="g">pages:87-96</subfield><subfield code="g">extent:10</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1016/j.biochi.2017.11.013</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ELV</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_U</subfield></datafield><datafield tag="936" ind1="b" ind2="k"><subfield code="a">50.70</subfield><subfield code="j">Energie: Allgemeines</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">146</subfield><subfield code="j">2018</subfield><subfield code="h">87-96</subfield><subfield code="g">10</subfield></datafield></record></collection>
|
| author |
de Barros, Andrea C. |
| spellingShingle |
de Barros, Andrea C. ddc 600 bkl 50.70 Elsevier X-ray crystallography Elsevier Nuclear localization sequence (NLS) Elsevier Importin-α Elsevier Nuclear import pathway Elsevier MLH1 and PMS2 proteins Elsevier Isothermal titration calorimetry Elsevier DNA repair DNA mismatch repair proteins MLH1 and PMS2 can be imported to the nucleus by a classical nuclear import pathway |
| authorStr |
de Barros, Andrea C. |
| ppnlink_with_tag_str_mv |
@@773@@(DE-627)ELV008857954 |
| format |
electronic Article |
| dewey-ones |
600 - Technology |
| delete_txt_mv |
keep |
| author_role |
aut |
| collection |
elsevier |
| remote_str |
true |
| illustrated |
Not Illustrated |
| topic_title |
600 VZ 50.70 bkl DNA mismatch repair proteins MLH1 and PMS2 can be imported to the nucleus by a classical nuclear import pathway X-ray crystallography Elsevier Nuclear localization sequence (NLS) Elsevier Importin-α Elsevier Nuclear import pathway Elsevier MLH1 and PMS2 proteins Elsevier Isothermal titration calorimetry Elsevier DNA repair Elsevier |
| topic |
ddc 600 bkl 50.70 Elsevier X-ray crystallography Elsevier Nuclear localization sequence (NLS) Elsevier Importin-α Elsevier Nuclear import pathway Elsevier MLH1 and PMS2 proteins Elsevier Isothermal titration calorimetry Elsevier DNA repair |
| topic_unstemmed |
ddc 600 bkl 50.70 Elsevier X-ray crystallography Elsevier Nuclear localization sequence (NLS) Elsevier Importin-α Elsevier Nuclear import pathway Elsevier MLH1 and PMS2 proteins Elsevier Isothermal titration calorimetry Elsevier DNA repair |
| topic_browse |
ddc 600 bkl 50.70 Elsevier X-ray crystallography Elsevier Nuclear localization sequence (NLS) Elsevier Importin-α Elsevier Nuclear import pathway Elsevier MLH1 and PMS2 proteins Elsevier Isothermal titration calorimetry Elsevier DNA repair |
| format_facet |
Elektronische Aufsätze Aufsätze Elektronische Ressource |
| format_main_str_mv |
Text Zeitschrift/Artikel |
| carriertype_str_mv |
zu |
| author2_variant |
a a t aa aat t r d tr trd a v c avc b k bk m r f mr mrf |
| hierarchy_parent_title |
Energy-saving improvement of heat integration for separating dilute azeotropic components in extractive distillation |
| hierarchy_parent_id |
ELV008857954 |
| dewey-tens |
600 - Technology |
| hierarchy_top_title |
Energy-saving improvement of heat integration for separating dilute azeotropic components in extractive distillation |
| isfreeaccess_txt |
false |
| familylinks_str_mv |
(DE-627)ELV008857954 |
| title |
DNA mismatch repair proteins MLH1 and PMS2 can be imported to the nucleus by a classical nuclear import pathway |
| ctrlnum |
(DE-627)ELV041896556 (ELSEVIER)S0300-9084(17)30308-5 |
| title_full |
DNA mismatch repair proteins MLH1 and PMS2 can be imported to the nucleus by a classical nuclear import pathway |
| author_sort |
de Barros, Andrea C. |
| journal |
Energy-saving improvement of heat integration for separating dilute azeotropic components in extractive distillation |
| journalStr |
Energy-saving improvement of heat integration for separating dilute azeotropic components in extractive distillation |
| lang_code |
eng |
| isOA_bool |
false |
| dewey-hundreds |
600 - Technology |
| recordtype |
marc |
| publishDateSort |
2018 |
| contenttype_str_mv |
zzz |
| container_start_page |
87 |
| author_browse |
de Barros, Andrea C. |
| container_volume |
146 |
| physical |
10 |
| class |
600 VZ 50.70 bkl |
| format_se |
Elektronische Aufsätze |
| author-letter |
de Barros, Andrea C. |
| doi_str_mv |
10.1016/j.biochi.2017.11.013 |
| dewey-full |
600 |
| title_sort |
dna mismatch repair proteins mlh1 and pms2 can be imported to the nucleus by a classical nuclear import pathway |
| title_auth |
DNA mismatch repair proteins MLH1 and PMS2 can be imported to the nucleus by a classical nuclear import pathway |
| abstract |
MLH1 and PMS2 proteins form the MutLα heterodimer, which plays a major role in DNA mismatch repair (MMR) in humans. Mutations in MMR-related proteins are associated with cancer, especially with colon cancer. The N-terminal region of MutLα comprises the N-termini of PMS2 and MLH1 and, similarly, the C-terminal region of MutLα is composed by the C-termini of PMS2 and MLH1, and the two are connected by linker region. The nuclear localization sequences (NLSs) necessary for the nuclear transport of the two proteins are found in this linker region. However, the exact NLS sequences have been controversial, with different sequences reported, particularly for MLH1. The individual components are not imported efficiently, presumably due to their C-termini masking their NLSs. In order to gain insights into the nuclear transport of these proteins, we solved the crystal structures of importin-α bound to peptides corresponding to the supposed NLSs of MLH1 and PMS2 and performed isothermal titration calorimetry to study their binding affinities. Both putative MLH1 and PMS2 NLSs can bind to importin-α as monopartite NLSs, which is in agreement with some previous studies. However, MLH1-NLS has the highest affinity measured by a natural NLS peptide, suggesting a major role of MLH1 protein in nuclear import compared to PMS2. Finally, the role of MLH1 and PMS2 in the nuclear transport of the MutLα heterodimer is discussed. |
| abstractGer |
MLH1 and PMS2 proteins form the MutLα heterodimer, which plays a major role in DNA mismatch repair (MMR) in humans. Mutations in MMR-related proteins are associated with cancer, especially with colon cancer. The N-terminal region of MutLα comprises the N-termini of PMS2 and MLH1 and, similarly, the C-terminal region of MutLα is composed by the C-termini of PMS2 and MLH1, and the two are connected by linker region. The nuclear localization sequences (NLSs) necessary for the nuclear transport of the two proteins are found in this linker region. However, the exact NLS sequences have been controversial, with different sequences reported, particularly for MLH1. The individual components are not imported efficiently, presumably due to their C-termini masking their NLSs. In order to gain insights into the nuclear transport of these proteins, we solved the crystal structures of importin-α bound to peptides corresponding to the supposed NLSs of MLH1 and PMS2 and performed isothermal titration calorimetry to study their binding affinities. Both putative MLH1 and PMS2 NLSs can bind to importin-α as monopartite NLSs, which is in agreement with some previous studies. However, MLH1-NLS has the highest affinity measured by a natural NLS peptide, suggesting a major role of MLH1 protein in nuclear import compared to PMS2. Finally, the role of MLH1 and PMS2 in the nuclear transport of the MutLα heterodimer is discussed. |
| abstract_unstemmed |
MLH1 and PMS2 proteins form the MutLα heterodimer, which plays a major role in DNA mismatch repair (MMR) in humans. Mutations in MMR-related proteins are associated with cancer, especially with colon cancer. The N-terminal region of MutLα comprises the N-termini of PMS2 and MLH1 and, similarly, the C-terminal region of MutLα is composed by the C-termini of PMS2 and MLH1, and the two are connected by linker region. The nuclear localization sequences (NLSs) necessary for the nuclear transport of the two proteins are found in this linker region. However, the exact NLS sequences have been controversial, with different sequences reported, particularly for MLH1. The individual components are not imported efficiently, presumably due to their C-termini masking their NLSs. In order to gain insights into the nuclear transport of these proteins, we solved the crystal structures of importin-α bound to peptides corresponding to the supposed NLSs of MLH1 and PMS2 and performed isothermal titration calorimetry to study their binding affinities. Both putative MLH1 and PMS2 NLSs can bind to importin-α as monopartite NLSs, which is in agreement with some previous studies. However, MLH1-NLS has the highest affinity measured by a natural NLS peptide, suggesting a major role of MLH1 protein in nuclear import compared to PMS2. Finally, the role of MLH1 and PMS2 in the nuclear transport of the MutLα heterodimer is discussed. |
| collection_details |
GBV_USEFLAG_U GBV_ELV SYSFLAG_U |
| title_short |
DNA mismatch repair proteins MLH1 and PMS2 can be imported to the nucleus by a classical nuclear import pathway |
| url |
https://doi.org/10.1016/j.biochi.2017.11.013 |
| remote_bool |
true |
| author2 |
Takeda, Agnes A.S. Dreyer, Thiago R. Velazquez-Campoy, Adrian Kobe, Boštjan Fontes, Marcos R.M. |
| author2Str |
Takeda, Agnes A.S. Dreyer, Thiago R. Velazquez-Campoy, Adrian Kobe, Boštjan Fontes, Marcos R.M. |
| ppnlink |
ELV008857954 |
| mediatype_str_mv |
z |
| isOA_txt |
false |
| hochschulschrift_bool |
false |
| author2_role |
oth oth oth oth oth |
| doi_str |
10.1016/j.biochi.2017.11.013 |
| up_date |
2024-07-06T21:21:58.521Z |
| _version_ |
1803866255940124672 |
| fullrecord_marcxml |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">ELV041896556</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230625235943.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">180726s2018 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.biochi.2017.11.013</subfield><subfield code="2">doi</subfield></datafield><datafield tag="028" ind1="5" ind2="2"><subfield code="a">GBV00000000000506.pica</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)ELV041896556</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(ELSEVIER)S0300-9084(17)30308-5</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">600</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">50.70</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">de Barros, Andrea C.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">DNA mismatch repair proteins MLH1 and PMS2 can be imported to the nucleus by a classical nuclear import pathway</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2018transfer abstract</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">10</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zzz</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">z</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zu</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">MLH1 and PMS2 proteins form the MutLα heterodimer, which plays a major role in DNA mismatch repair (MMR) in humans. Mutations in MMR-related proteins are associated with cancer, especially with colon cancer. The N-terminal region of MutLα comprises the N-termini of PMS2 and MLH1 and, similarly, the C-terminal region of MutLα is composed by the C-termini of PMS2 and MLH1, and the two are connected by linker region. The nuclear localization sequences (NLSs) necessary for the nuclear transport of the two proteins are found in this linker region. However, the exact NLS sequences have been controversial, with different sequences reported, particularly for MLH1. The individual components are not imported efficiently, presumably due to their C-termini masking their NLSs. In order to gain insights into the nuclear transport of these proteins, we solved the crystal structures of importin-α bound to peptides corresponding to the supposed NLSs of MLH1 and PMS2 and performed isothermal titration calorimetry to study their binding affinities. Both putative MLH1 and PMS2 NLSs can bind to importin-α as monopartite NLSs, which is in agreement with some previous studies. However, MLH1-NLS has the highest affinity measured by a natural NLS peptide, suggesting a major role of MLH1 protein in nuclear import compared to PMS2. Finally, the role of MLH1 and PMS2 in the nuclear transport of the MutLα heterodimer is discussed.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">MLH1 and PMS2 proteins form the MutLα heterodimer, which plays a major role in DNA mismatch repair (MMR) in humans. Mutations in MMR-related proteins are associated with cancer, especially with colon cancer. The N-terminal region of MutLα comprises the N-termini of PMS2 and MLH1 and, similarly, the C-terminal region of MutLα is composed by the C-termini of PMS2 and MLH1, and the two are connected by linker region. The nuclear localization sequences (NLSs) necessary for the nuclear transport of the two proteins are found in this linker region. However, the exact NLS sequences have been controversial, with different sequences reported, particularly for MLH1. The individual components are not imported efficiently, presumably due to their C-termini masking their NLSs. In order to gain insights into the nuclear transport of these proteins, we solved the crystal structures of importin-α bound to peptides corresponding to the supposed NLSs of MLH1 and PMS2 and performed isothermal titration calorimetry to study their binding affinities. Both putative MLH1 and PMS2 NLSs can bind to importin-α as monopartite NLSs, which is in agreement with some previous studies. However, MLH1-NLS has the highest affinity measured by a natural NLS peptide, suggesting a major role of MLH1 protein in nuclear import compared to PMS2. Finally, the role of MLH1 and PMS2 in the nuclear transport of the MutLα heterodimer is discussed.</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">X-ray crystallography</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Nuclear localization sequence (NLS)</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Importin-α</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Nuclear import pathway</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">MLH1 and PMS2 proteins</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Isothermal titration calorimetry</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">DNA repair</subfield><subfield code="2">Elsevier</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Takeda, Agnes A.S.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Dreyer, Thiago R.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Velazquez-Campoy, Adrian</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Kobe, Boštjan</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Fontes, Marcos R.M.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="n">Elsevier</subfield><subfield code="a">Duan, Cong ELSEVIER</subfield><subfield code="t">Energy-saving improvement of heat integration for separating dilute azeotropic components in extractive distillation</subfield><subfield code="d">2022</subfield><subfield code="d">an international journal of biochemistry and molecular biology</subfield><subfield code="g">Paris [u.a.]</subfield><subfield code="w">(DE-627)ELV008857954</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:146</subfield><subfield code="g">year:2018</subfield><subfield code="g">pages:87-96</subfield><subfield code="g">extent:10</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1016/j.biochi.2017.11.013</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ELV</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_U</subfield></datafield><datafield tag="936" ind1="b" ind2="k"><subfield code="a">50.70</subfield><subfield code="j">Energie: Allgemeines</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">146</subfield><subfield code="j">2018</subfield><subfield code="h">87-96</subfield><subfield code="g">10</subfield></datafield></record></collection>
|
| score |
7.4003716 |