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
Autor*in: |
de Barros, Andrea C. [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2018transfer abstract |
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Schlagwörter: |
Nuclear localization sequence (NLS) |
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Umfang: |
10 |
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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.] |
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Übergeordnetes Werk: |
volume:146 ; year:2018 ; pages:87-96 ; extent:10 |
Links: |
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DOI / URN: |
10.1016/j.biochi.2017.11.013 |
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Katalog-ID: |
ELV041896556 |
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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 | |
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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 |
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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 |
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Energy-saving improvement of heat integration for separating dilute azeotropic components in extractive distillation |
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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 |
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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 |
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de Barros, Andrea C. |
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dna mismatch repair proteins mlh1 and pms2 can be imported to the nucleus by a classical nuclear import pathway |
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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. |
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DNA mismatch repair proteins MLH1 and PMS2 can be imported to the nucleus by a classical nuclear import pathway |
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