The crystal structure of the phosphatidylinositol 4‐kinase IIα
Abstract Phosphoinositides are a class of phospholipids generated by the action of phosphoinositide kinases with key regulatory functions in eukaryotic cells. Here, we present the atomic structure of phosphatidylinositol 4‐kinase type IIα (PI4K IIα), in complex with ATP solved by X‐ray crystallograp...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Baumlova, Adriana [verfasserIn] Chalupska, Dominika [verfasserIn] Róźycki, Bartosz [verfasserIn] Jovic, Marko [verfasserIn] Wisniewski, Eva [verfasserIn] Klima, Martin [verfasserIn] Dubankova, Anna [verfasserIn] Kloer, Daniel P [verfasserIn] Nencka, Radim [verfasserIn] Balla, Tamas [verfasserIn] Boura, Evzen [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2014 |
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| Schlagwörter: |
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| Anmerkung: |
© The Author(s) 2014 |
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| Übergeordnetes Werk: |
Enthalten in: EMBO Reports - Nature Publishing Group UK, 2023, 15(2014), 10 vom: 28. Aug., Seite 1085-1092 |
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| Übergeordnetes Werk: |
volume:15 ; year:2014 ; number:10 ; day:28 ; month:08 ; pages:1085-1092 |
| Links: |
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| DOI / URN: |
10.15252/embr.201438841 |
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| Katalog-ID: |
SPR05802526X |
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| 100 | 1 | |a Baumlova, Adriana |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a The crystal structure of the phosphatidylinositol 4‐kinase IIα |
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| 520 | |a Abstract Phosphoinositides are a class of phospholipids generated by the action of phosphoinositide kinases with key regulatory functions in eukaryotic cells. Here, we present the atomic structure of phosphatidylinositol 4‐kinase type IIα (PI4K IIα), in complex with ATP solved by X‐ray crystallography at 2.8 Å resolution. The structure revealed a non‐typical kinase fold that could be divided into N‐ and C‐lobes with the ATP binding groove located in between. Surprisingly, a second ATP was found in a lateral hydrophobic pocket of the C‐lobe. Molecular simulations and mutagenesis analysis revealed the membrane binding mode and the putative function of the hydrophobic pocket. Taken together, our results suggest a mechanism of PI4K IIα recruitment, regulation, and function at the membrane. | ||
| 520 | |a Synopsis The crystal structure of PI4K IIα reveals its membrane binding mode and highlights a membrane‐oriented hydrophobic pocket as a potential allosteric regulatory site. The crystal structure of PI4K IIα was solved at 2.8 Å resolution.The structure highlights important differences between type II and type III PI 4‐kinases.Molecular simulation suggests a membrane binding mode that involves a hydrophobic pocket with allosteric regulatory potential. | ||
| 520 | |a Graphical Abstract The crystal structure of PI4K IIα reveals its membrane binding mode and highlights a membrane‐oriented hydrophobic pocket as a potential allosteric regulatory site. | ||
| 650 | 4 | |a crystal structure |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a kinase |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a membrane |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Monte Carlo simulations |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a phosphatidyl inositol |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Chalupska, Dominika |e verfasserin |4 aut | |
| 700 | 1 | |a Róźycki, Bartosz |e verfasserin |4 aut | |
| 700 | 1 | |a Jovic, Marko |e verfasserin |4 aut | |
| 700 | 1 | |a Wisniewski, Eva |e verfasserin |4 aut | |
| 700 | 1 | |a Klima, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Dubankova, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Kloer, Daniel P |e verfasserin |4 aut | |
| 700 | 1 | |a Nencka, Radim |e verfasserin |4 aut | |
| 700 | 1 | |a Balla, Tamas |e verfasserin |4 aut | |
| 700 | 1 | |a Boura, Evzen |e verfasserin |4 aut | |
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10.15252/embr.201438841 doi (DE-627)SPR05802526X (SPR)embr.201438841-e DE-627 ger DE-627 rakwb eng Baumlova, Adriana verfasserin aut The crystal structure of the phosphatidylinositol 4‐kinase IIα 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2014 Abstract Phosphoinositides are a class of phospholipids generated by the action of phosphoinositide kinases with key regulatory functions in eukaryotic cells. Here, we present the atomic structure of phosphatidylinositol 4‐kinase type IIα (PI4K IIα), in complex with ATP solved by X‐ray crystallography at 2.8 Å resolution. The structure revealed a non‐typical kinase fold that could be divided into N‐ and C‐lobes with the ATP binding groove located in between. Surprisingly, a second ATP was found in a lateral hydrophobic pocket of the C‐lobe. Molecular simulations and mutagenesis analysis revealed the membrane binding mode and the putative function of the hydrophobic pocket. Taken together, our results suggest a mechanism of PI4K IIα recruitment, regulation, and function at the membrane. Synopsis The crystal structure of PI4K IIα reveals its membrane binding mode and highlights a membrane‐oriented hydrophobic pocket as a potential allosteric regulatory site. The crystal structure of PI4K IIα was solved at 2.8 Å resolution.The structure highlights important differences between type II and type III PI 4‐kinases.Molecular simulation suggests a membrane binding mode that involves a hydrophobic pocket with allosteric regulatory potential. Graphical Abstract The crystal structure of PI4K IIα reveals its membrane binding mode and highlights a membrane‐oriented hydrophobic pocket as a potential allosteric regulatory site. crystal structure (dpeaa)DE-He213 kinase (dpeaa)DE-He213 membrane (dpeaa)DE-He213 Monte Carlo simulations (dpeaa)DE-He213 phosphatidyl inositol (dpeaa)DE-He213 Chalupska, Dominika verfasserin aut Róźycki, Bartosz verfasserin aut Jovic, Marko verfasserin aut Wisniewski, Eva verfasserin aut Klima, Martin verfasserin aut Dubankova, Anna verfasserin aut Kloer, Daniel P verfasserin aut Nencka, Radim verfasserin aut Balla, Tamas verfasserin aut Boura, Evzen verfasserin aut Enthalten in EMBO Reports Nature Publishing Group UK, 2023 15(2014), 10 vom: 28. Aug., Seite 1085-1092 (DE-627)320645622 (DE-600)2025376-X 1469-3178 nnns volume:15 year:2014 number:10 day:28 month:08 pages:1085-1092 https://dx.doi.org/10.15252/embr.201438841 X:SPRINGER Resolving-System lizenzpflichtig Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 15 2014 10 28 08 1085-1092 |
| spelling |
10.15252/embr.201438841 doi (DE-627)SPR05802526X (SPR)embr.201438841-e DE-627 ger DE-627 rakwb eng Baumlova, Adriana verfasserin aut The crystal structure of the phosphatidylinositol 4‐kinase IIα 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2014 Abstract Phosphoinositides are a class of phospholipids generated by the action of phosphoinositide kinases with key regulatory functions in eukaryotic cells. Here, we present the atomic structure of phosphatidylinositol 4‐kinase type IIα (PI4K IIα), in complex with ATP solved by X‐ray crystallography at 2.8 Å resolution. The structure revealed a non‐typical kinase fold that could be divided into N‐ and C‐lobes with the ATP binding groove located in between. Surprisingly, a second ATP was found in a lateral hydrophobic pocket of the C‐lobe. Molecular simulations and mutagenesis analysis revealed the membrane binding mode and the putative function of the hydrophobic pocket. Taken together, our results suggest a mechanism of PI4K IIα recruitment, regulation, and function at the membrane. Synopsis The crystal structure of PI4K IIα reveals its membrane binding mode and highlights a membrane‐oriented hydrophobic pocket as a potential allosteric regulatory site. The crystal structure of PI4K IIα was solved at 2.8 Å resolution.The structure highlights important differences between type II and type III PI 4‐kinases.Molecular simulation suggests a membrane binding mode that involves a hydrophobic pocket with allosteric regulatory potential. Graphical Abstract The crystal structure of PI4K IIα reveals its membrane binding mode and highlights a membrane‐oriented hydrophobic pocket as a potential allosteric regulatory site. crystal structure (dpeaa)DE-He213 kinase (dpeaa)DE-He213 membrane (dpeaa)DE-He213 Monte Carlo simulations (dpeaa)DE-He213 phosphatidyl inositol (dpeaa)DE-He213 Chalupska, Dominika verfasserin aut Róźycki, Bartosz verfasserin aut Jovic, Marko verfasserin aut Wisniewski, Eva verfasserin aut Klima, Martin verfasserin aut Dubankova, Anna verfasserin aut Kloer, Daniel P verfasserin aut Nencka, Radim verfasserin aut Balla, Tamas verfasserin aut Boura, Evzen verfasserin aut Enthalten in EMBO Reports Nature Publishing Group UK, 2023 15(2014), 10 vom: 28. Aug., Seite 1085-1092 (DE-627)320645622 (DE-600)2025376-X 1469-3178 nnns volume:15 year:2014 number:10 day:28 month:08 pages:1085-1092 https://dx.doi.org/10.15252/embr.201438841 X:SPRINGER Resolving-System lizenzpflichtig Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 15 2014 10 28 08 1085-1092 |
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10.15252/embr.201438841 doi (DE-627)SPR05802526X (SPR)embr.201438841-e DE-627 ger DE-627 rakwb eng Baumlova, Adriana verfasserin aut The crystal structure of the phosphatidylinositol 4‐kinase IIα 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2014 Abstract Phosphoinositides are a class of phospholipids generated by the action of phosphoinositide kinases with key regulatory functions in eukaryotic cells. Here, we present the atomic structure of phosphatidylinositol 4‐kinase type IIα (PI4K IIα), in complex with ATP solved by X‐ray crystallography at 2.8 Å resolution. The structure revealed a non‐typical kinase fold that could be divided into N‐ and C‐lobes with the ATP binding groove located in between. Surprisingly, a second ATP was found in a lateral hydrophobic pocket of the C‐lobe. Molecular simulations and mutagenesis analysis revealed the membrane binding mode and the putative function of the hydrophobic pocket. Taken together, our results suggest a mechanism of PI4K IIα recruitment, regulation, and function at the membrane. Synopsis The crystal structure of PI4K IIα reveals its membrane binding mode and highlights a membrane‐oriented hydrophobic pocket as a potential allosteric regulatory site. The crystal structure of PI4K IIα was solved at 2.8 Å resolution.The structure highlights important differences between type II and type III PI 4‐kinases.Molecular simulation suggests a membrane binding mode that involves a hydrophobic pocket with allosteric regulatory potential. Graphical Abstract The crystal structure of PI4K IIα reveals its membrane binding mode and highlights a membrane‐oriented hydrophobic pocket as a potential allosteric regulatory site. crystal structure (dpeaa)DE-He213 kinase (dpeaa)DE-He213 membrane (dpeaa)DE-He213 Monte Carlo simulations (dpeaa)DE-He213 phosphatidyl inositol (dpeaa)DE-He213 Chalupska, Dominika verfasserin aut Róźycki, Bartosz verfasserin aut Jovic, Marko verfasserin aut Wisniewski, Eva verfasserin aut Klima, Martin verfasserin aut Dubankova, Anna verfasserin aut Kloer, Daniel P verfasserin aut Nencka, Radim verfasserin aut Balla, Tamas verfasserin aut Boura, Evzen verfasserin aut Enthalten in EMBO Reports Nature Publishing Group UK, 2023 15(2014), 10 vom: 28. Aug., Seite 1085-1092 (DE-627)320645622 (DE-600)2025376-X 1469-3178 nnns volume:15 year:2014 number:10 day:28 month:08 pages:1085-1092 https://dx.doi.org/10.15252/embr.201438841 X:SPRINGER Resolving-System lizenzpflichtig Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 15 2014 10 28 08 1085-1092 |
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10.15252/embr.201438841 doi (DE-627)SPR05802526X (SPR)embr.201438841-e DE-627 ger DE-627 rakwb eng Baumlova, Adriana verfasserin aut The crystal structure of the phosphatidylinositol 4‐kinase IIα 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2014 Abstract Phosphoinositides are a class of phospholipids generated by the action of phosphoinositide kinases with key regulatory functions in eukaryotic cells. Here, we present the atomic structure of phosphatidylinositol 4‐kinase type IIα (PI4K IIα), in complex with ATP solved by X‐ray crystallography at 2.8 Å resolution. The structure revealed a non‐typical kinase fold that could be divided into N‐ and C‐lobes with the ATP binding groove located in between. Surprisingly, a second ATP was found in a lateral hydrophobic pocket of the C‐lobe. Molecular simulations and mutagenesis analysis revealed the membrane binding mode and the putative function of the hydrophobic pocket. Taken together, our results suggest a mechanism of PI4K IIα recruitment, regulation, and function at the membrane. Synopsis The crystal structure of PI4K IIα reveals its membrane binding mode and highlights a membrane‐oriented hydrophobic pocket as a potential allosteric regulatory site. The crystal structure of PI4K IIα was solved at 2.8 Å resolution.The structure highlights important differences between type II and type III PI 4‐kinases.Molecular simulation suggests a membrane binding mode that involves a hydrophobic pocket with allosteric regulatory potential. Graphical Abstract The crystal structure of PI4K IIα reveals its membrane binding mode and highlights a membrane‐oriented hydrophobic pocket as a potential allosteric regulatory site. crystal structure (dpeaa)DE-He213 kinase (dpeaa)DE-He213 membrane (dpeaa)DE-He213 Monte Carlo simulations (dpeaa)DE-He213 phosphatidyl inositol (dpeaa)DE-He213 Chalupska, Dominika verfasserin aut Róźycki, Bartosz verfasserin aut Jovic, Marko verfasserin aut Wisniewski, Eva verfasserin aut Klima, Martin verfasserin aut Dubankova, Anna verfasserin aut Kloer, Daniel P verfasserin aut Nencka, Radim verfasserin aut Balla, Tamas verfasserin aut Boura, Evzen verfasserin aut Enthalten in EMBO Reports Nature Publishing Group UK, 2023 15(2014), 10 vom: 28. Aug., Seite 1085-1092 (DE-627)320645622 (DE-600)2025376-X 1469-3178 nnns volume:15 year:2014 number:10 day:28 month:08 pages:1085-1092 https://dx.doi.org/10.15252/embr.201438841 X:SPRINGER Resolving-System lizenzpflichtig Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 15 2014 10 28 08 1085-1092 |
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10.15252/embr.201438841 doi (DE-627)SPR05802526X (SPR)embr.201438841-e DE-627 ger DE-627 rakwb eng Baumlova, Adriana verfasserin aut The crystal structure of the phosphatidylinositol 4‐kinase IIα 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2014 Abstract Phosphoinositides are a class of phospholipids generated by the action of phosphoinositide kinases with key regulatory functions in eukaryotic cells. Here, we present the atomic structure of phosphatidylinositol 4‐kinase type IIα (PI4K IIα), in complex with ATP solved by X‐ray crystallography at 2.8 Å resolution. The structure revealed a non‐typical kinase fold that could be divided into N‐ and C‐lobes with the ATP binding groove located in between. Surprisingly, a second ATP was found in a lateral hydrophobic pocket of the C‐lobe. Molecular simulations and mutagenesis analysis revealed the membrane binding mode and the putative function of the hydrophobic pocket. Taken together, our results suggest a mechanism of PI4K IIα recruitment, regulation, and function at the membrane. Synopsis The crystal structure of PI4K IIα reveals its membrane binding mode and highlights a membrane‐oriented hydrophobic pocket as a potential allosteric regulatory site. The crystal structure of PI4K IIα was solved at 2.8 Å resolution.The structure highlights important differences between type II and type III PI 4‐kinases.Molecular simulation suggests a membrane binding mode that involves a hydrophobic pocket with allosteric regulatory potential. Graphical Abstract The crystal structure of PI4K IIα reveals its membrane binding mode and highlights a membrane‐oriented hydrophobic pocket as a potential allosteric regulatory site. crystal structure (dpeaa)DE-He213 kinase (dpeaa)DE-He213 membrane (dpeaa)DE-He213 Monte Carlo simulations (dpeaa)DE-He213 phosphatidyl inositol (dpeaa)DE-He213 Chalupska, Dominika verfasserin aut Róźycki, Bartosz verfasserin aut Jovic, Marko verfasserin aut Wisniewski, Eva verfasserin aut Klima, Martin verfasserin aut Dubankova, Anna verfasserin aut Kloer, Daniel P verfasserin aut Nencka, Radim verfasserin aut Balla, Tamas verfasserin aut Boura, Evzen verfasserin aut Enthalten in EMBO Reports Nature Publishing Group UK, 2023 15(2014), 10 vom: 28. Aug., Seite 1085-1092 (DE-627)320645622 (DE-600)2025376-X 1469-3178 nnns volume:15 year:2014 number:10 day:28 month:08 pages:1085-1092 https://dx.doi.org/10.15252/embr.201438841 X:SPRINGER Resolving-System lizenzpflichtig Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 15 2014 10 28 08 1085-1092 |
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Enthalten in EMBO Reports 15(2014), 10 vom: 28. Aug., Seite 1085-1092 volume:15 year:2014 number:10 day:28 month:08 pages:1085-1092 |
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Baumlova, Adriana @@aut@@ Chalupska, Dominika @@aut@@ Róźycki, Bartosz @@aut@@ Jovic, Marko @@aut@@ Wisniewski, Eva @@aut@@ Klima, Martin @@aut@@ Dubankova, Anna @@aut@@ Kloer, Daniel P @@aut@@ Nencka, Radim @@aut@@ Balla, Tamas @@aut@@ Boura, Evzen @@aut@@ |
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Here, we present the atomic structure of phosphatidylinositol 4‐kinase type IIα (PI4K IIα), in complex with ATP solved by X‐ray crystallography at 2.8 Å resolution. The structure revealed a non‐typical kinase fold that could be divided into N‐ and C‐lobes with the ATP binding groove located in between. Surprisingly, a second ATP was found in a lateral hydrophobic pocket of the C‐lobe. Molecular simulations and mutagenesis analysis revealed the membrane binding mode and the putative function of the hydrophobic pocket. Taken together, our results suggest a mechanism of PI4K IIα recruitment, regulation, and function at the membrane.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Synopsis The crystal structure of PI4K IIα reveals its membrane binding mode and highlights a membrane‐oriented hydrophobic pocket as a potential allosteric regulatory site. 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Baumlova, Adriana |
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Baumlova, Adriana misc crystal structure misc kinase misc membrane misc Monte Carlo simulations misc phosphatidyl inositol The crystal structure of the phosphatidylinositol 4‐kinase IIα |
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The crystal structure of the phosphatidylinositol 4‐kinase IIα crystal structure (dpeaa)DE-He213 kinase (dpeaa)DE-He213 membrane (dpeaa)DE-He213 Monte Carlo simulations (dpeaa)DE-He213 phosphatidyl inositol (dpeaa)DE-He213 |
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Baumlova, Adriana Chalupska, Dominika Róźycki, Bartosz Jovic, Marko Wisniewski, Eva Klima, Martin Dubankova, Anna Kloer, Daniel P Nencka, Radim Balla, Tamas Boura, Evzen |
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Elektronische Aufsätze |
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Baumlova, Adriana |
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10.15252/embr.201438841 |
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verfasserin |
| title_sort |
the crystal structure of the phosphatidylinositol 4‐kinase iiα |
| title_auth |
The crystal structure of the phosphatidylinositol 4‐kinase IIα |
| abstract |
Abstract Phosphoinositides are a class of phospholipids generated by the action of phosphoinositide kinases with key regulatory functions in eukaryotic cells. Here, we present the atomic structure of phosphatidylinositol 4‐kinase type IIα (PI4K IIα), in complex with ATP solved by X‐ray crystallography at 2.8 Å resolution. The structure revealed a non‐typical kinase fold that could be divided into N‐ and C‐lobes with the ATP binding groove located in between. Surprisingly, a second ATP was found in a lateral hydrophobic pocket of the C‐lobe. Molecular simulations and mutagenesis analysis revealed the membrane binding mode and the putative function of the hydrophobic pocket. Taken together, our results suggest a mechanism of PI4K IIα recruitment, regulation, and function at the membrane. Synopsis The crystal structure of PI4K IIα reveals its membrane binding mode and highlights a membrane‐oriented hydrophobic pocket as a potential allosteric regulatory site. The crystal structure of PI4K IIα was solved at 2.8 Å resolution.The structure highlights important differences between type II and type III PI 4‐kinases.Molecular simulation suggests a membrane binding mode that involves a hydrophobic pocket with allosteric regulatory potential. Graphical Abstract The crystal structure of PI4K IIα reveals its membrane binding mode and highlights a membrane‐oriented hydrophobic pocket as a potential allosteric regulatory site. © The Author(s) 2014 |
| abstractGer |
Abstract Phosphoinositides are a class of phospholipids generated by the action of phosphoinositide kinases with key regulatory functions in eukaryotic cells. Here, we present the atomic structure of phosphatidylinositol 4‐kinase type IIα (PI4K IIα), in complex with ATP solved by X‐ray crystallography at 2.8 Å resolution. The structure revealed a non‐typical kinase fold that could be divided into N‐ and C‐lobes with the ATP binding groove located in between. Surprisingly, a second ATP was found in a lateral hydrophobic pocket of the C‐lobe. Molecular simulations and mutagenesis analysis revealed the membrane binding mode and the putative function of the hydrophobic pocket. Taken together, our results suggest a mechanism of PI4K IIα recruitment, regulation, and function at the membrane. Synopsis The crystal structure of PI4K IIα reveals its membrane binding mode and highlights a membrane‐oriented hydrophobic pocket as a potential allosteric regulatory site. The crystal structure of PI4K IIα was solved at 2.8 Å resolution.The structure highlights important differences between type II and type III PI 4‐kinases.Molecular simulation suggests a membrane binding mode that involves a hydrophobic pocket with allosteric regulatory potential. Graphical Abstract The crystal structure of PI4K IIα reveals its membrane binding mode and highlights a membrane‐oriented hydrophobic pocket as a potential allosteric regulatory site. © The Author(s) 2014 |
| abstract_unstemmed |
Abstract Phosphoinositides are a class of phospholipids generated by the action of phosphoinositide kinases with key regulatory functions in eukaryotic cells. Here, we present the atomic structure of phosphatidylinositol 4‐kinase type IIα (PI4K IIα), in complex with ATP solved by X‐ray crystallography at 2.8 Å resolution. The structure revealed a non‐typical kinase fold that could be divided into N‐ and C‐lobes with the ATP binding groove located in between. Surprisingly, a second ATP was found in a lateral hydrophobic pocket of the C‐lobe. Molecular simulations and mutagenesis analysis revealed the membrane binding mode and the putative function of the hydrophobic pocket. Taken together, our results suggest a mechanism of PI4K IIα recruitment, regulation, and function at the membrane. Synopsis The crystal structure of PI4K IIα reveals its membrane binding mode and highlights a membrane‐oriented hydrophobic pocket as a potential allosteric regulatory site. The crystal structure of PI4K IIα was solved at 2.8 Å resolution.The structure highlights important differences between type II and type III PI 4‐kinases.Molecular simulation suggests a membrane binding mode that involves a hydrophobic pocket with allosteric regulatory potential. Graphical Abstract The crystal structure of PI4K IIα reveals its membrane binding mode and highlights a membrane‐oriented hydrophobic pocket as a potential allosteric regulatory site. © The Author(s) 2014 |
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The crystal structure of the phosphatidylinositol 4‐kinase IIα |
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Chalupska, Dominika Róźycki, Bartosz Jovic, Marko Wisniewski, Eva Klima, Martin Dubankova, Anna Kloer, Daniel P Nencka, Radim Balla, Tamas Boura, Evzen |
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|
| score |
7.39966 |