2v76
From Proteopedia
(New page: 200px<br /><applet load="2v76" size="350" color="white" frame="true" align="right" spinBox="true" caption="2v76, resolution 1.60Å" /> '''CRYSTAL STRUCTURE OF...) |
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==Overview== | ==Overview== | ||
| - | Integrins play a fundamental role in cell migration and adhesion; | + | Integrins play a fundamental role in cell migration and adhesion; knowledge of how they are regulated and controlled is vital for understanding these processes. Recent work showed that Dok1 negatively regulates integrin activation, presumably by competition with talin. To understand how this occurs, we used NMR spectroscopy and X-ray crystallography to investigate the molecular details of interactions with integrins. The binding affinities of beta3 integrin tails for the Dok1 and talin PTB domains were quantified using 15N-1H HSQC titrations, revealing that the unphosphorylated integrin tail binds more strongly to talin than Dok1. Chemical shift mapping showed that unlike talin, Dok1 exclusively interacts with the canonical NPxY motif of the beta3 integrin tail. Upon phosphorylation of Tyr747 in the beta3 integrin tail, however, Dok1 then binds much more strongly than talin. Thus we show that phosphorylation of Tyr747 provides a switch for integrin ligand binding. This switch may represent an in vivo mechanism for control of integrin receptor activation. These results have implications for the control of integrin signaling by proteins containing PTB domains. |
==About this Structure== | ==About this Structure== | ||
| - | 2V76 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=PGE:'>PGE</scene>, <scene name='pdbligand=EDO:'>EDO</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Sites: <scene name='pdbsite=AC1:Pge Binding Site For Chain B'>AC1</scene>, <scene name='pdbsite=AC2:Pge Binding Site For Chain D'>AC2</scene>, <scene name='pdbsite=AC3:Pge Binding Site For Chain B'>AC3</scene>, <scene name='pdbsite=AC4:Pge Binding Site For Chain A'>AC4</scene>, <scene name='pdbsite=AC5:So4 Binding Site For Chain D'>AC5</scene>, <scene name='pdbsite=AC6:So4 Binding Site For Chain B'>AC6</scene>, <scene name='pdbsite=AC7:So4 Binding Site For Chain A'>AC7</scene>, <scene name='pdbsite=AC8:So4 Binding Site For Chain C'>AC8</scene>, <scene name='pdbsite=AC9:Gol Binding Site For Chain C'>AC9</scene> and <scene name='pdbsite=BC1:Edo Binding Site For Chain A'>BC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V76 OCA]. | + | 2V76 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=PGE:'>PGE</scene>, <scene name='pdbligand=EDO:'>EDO</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Sites: <scene name='pdbsite=AC1:Pge+Binding+Site+For+Chain+B'>AC1</scene>, <scene name='pdbsite=AC2:Pge+Binding+Site+For+Chain+D'>AC2</scene>, <scene name='pdbsite=AC3:Pge+Binding+Site+For+Chain+B'>AC3</scene>, <scene name='pdbsite=AC4:Pge+Binding+Site+For+Chain+A'>AC4</scene>, <scene name='pdbsite=AC5:So4+Binding+Site+For+Chain+D'>AC5</scene>, <scene name='pdbsite=AC6:So4+Binding+Site+For+Chain+B'>AC6</scene>, <scene name='pdbsite=AC7:So4+Binding+Site+For+Chain+A'>AC7</scene>, <scene name='pdbsite=AC8:So4+Binding+Site+For+Chain+C'>AC8</scene>, <scene name='pdbsite=AC9:Gol+Binding+Site+For+Chain+C'>AC9</scene> and <scene name='pdbsite=BC1:Edo+Binding+Site+For+Chain+A'>BC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V76 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Anthis, N | + | [[Category: Anthis, N J.]] |
| - | [[Category: Campbell, I | + | [[Category: Campbell, I D.]] |
| - | [[Category: Lowe, E | + | [[Category: Lowe, E D.]] |
| - | [[Category: Oxley, C | + | [[Category: Oxley, C L.]] |
| - | [[Category: Wegener, K | + | [[Category: Wegener, K L.]] |
[[Category: EDO]] | [[Category: EDO]] | ||
[[Category: GOL]] | [[Category: GOL]] | ||
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[[Category: ptb domain]] | [[Category: ptb domain]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:53:50 2008'' |
Revision as of 16:53, 21 February 2008
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CRYSTAL STRUCTURE OF THE HUMAN DOK1 PTB DOMAIN
Overview
Integrins play a fundamental role in cell migration and adhesion; knowledge of how they are regulated and controlled is vital for understanding these processes. Recent work showed that Dok1 negatively regulates integrin activation, presumably by competition with talin. To understand how this occurs, we used NMR spectroscopy and X-ray crystallography to investigate the molecular details of interactions with integrins. The binding affinities of beta3 integrin tails for the Dok1 and talin PTB domains were quantified using 15N-1H HSQC titrations, revealing that the unphosphorylated integrin tail binds more strongly to talin than Dok1. Chemical shift mapping showed that unlike talin, Dok1 exclusively interacts with the canonical NPxY motif of the beta3 integrin tail. Upon phosphorylation of Tyr747 in the beta3 integrin tail, however, Dok1 then binds much more strongly than talin. Thus we show that phosphorylation of Tyr747 provides a switch for integrin ligand binding. This switch may represent an in vivo mechanism for control of integrin receptor activation. These results have implications for the control of integrin signaling by proteins containing PTB domains.
About this Structure
2V76 is a Single protein structure of sequence from Homo sapiens with , , and as ligands. Known structural/functional Sites: , , , , , , , , and . Full crystallographic information is available from OCA.
Reference
An integrin phosphorylation switch: the effect of beta3 integrin tail phosphorylation on DOK1 and talin binding., Oxley CL, Anthis NJ, Lowe ED, Vakonakis I, Campbell ID, Wegener KL, J Biol Chem. 2007 Dec 21;. PMID:18156175
Page seeded by OCA on Thu Feb 21 18:53:50 2008
Categories: Homo sapiens | Single protein | Anthis, N J. | Campbell, I D. | Lowe, E D. | Oxley, C L. | Wegener, K L. | EDO | GOL | PGE | SO4 | Adaptor protein | Alternative splicing | Phosphorylation | Protein-binding | Ptb domain
