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| | ==Autoinhibited Vav1== | | ==Autoinhibited Vav1== |
| - | <StructureSection load='3ky9' size='340' side='right' caption='[[3ky9]], [[Resolution|resolution]] 2.73Å' scene=''> | + | <StructureSection load='3ky9' size='340' side='right'caption='[[3ky9]], [[Resolution|resolution]] 2.73Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3ky9]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KY9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KY9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3ky9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KY9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KY9 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.731Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VAV, VAV1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ky9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ky9 OCA], [http://pdbe.org/3ky9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ky9 RCSB], [http://www.ebi.ac.uk/pdbsum/3ky9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ky9 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3ky9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ky9 OCA], [https://pdbe.org/3ky9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ky9 RCSB], [https://www.ebi.ac.uk/pdbsum/3ky9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ky9 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/VAV_HUMAN VAV_HUMAN]] Couples tyrosine kinase signals with the activation of the Rho/Rac GTPases, thus leading to cell differentiation and/or proliferation. | + | [https://www.uniprot.org/uniprot/VAV_HUMAN VAV_HUMAN] Couples tyrosine kinase signals with the activation of the Rho/Rac GTPases, thus leading to cell differentiation and/or proliferation. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ky/3ky9_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ky/3ky9_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Machius, M]] | + | [[Category: Large Structures]] |
| - | [[Category: Rosen, M K]] | + | [[Category: Machius M]] |
| - | [[Category: Tomchick, D R]] | + | [[Category: Rosen MK]] |
| - | [[Category: Yu, B]] | + | [[Category: Tomchick DR]] |
| - | [[Category: Apoptosis]] | + | [[Category: Yu B]] |
| - | [[Category: C1 domain]]
| + | |
| - | [[Category: Calponin homology domain]]
| + | |
| - | [[Category: Dbl homology domain]]
| + | |
| - | [[Category: Guanine-nucleotide releasing factor]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Pleckstrin homology domain]]
| + | |
| - | [[Category: Proto-oncogene]]
| + | |
| - | [[Category: Sh2 domain]]
| + | |
| - | [[Category: Sh3 domain]]
| + | |
| - | [[Category: Vav1]]
| + | |
| - | [[Category: Zinc-finger]]
| + | |
| Structural highlights
Function
VAV_HUMAN Couples tyrosine kinase signals with the activation of the Rho/Rac GTPases, thus leading to cell differentiation and/or proliferation.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Vav proteins are guanine nucleotide exchange factors (GEFs) for Rho family GTPases. They control processes including T cell activation, phagocytosis, and migration of normal and transformed cells. We report the structure and biophysical and cellular analyses of the five-domain autoinhibitory element of Vav1. The catalytic Dbl homology (DH) domain of Vav1 is controlled by two energetically coupled processes. The DH active site is directly, but weakly, inhibited by a helix from the adjacent Acidic domain. This core interaction is strengthened 10-fold by contacts of the calponin homology (CH) domain with the Acidic, pleckstrin homology, and DH domains. This construction enables efficient, stepwise relief of autoinhibition: initial phosphorylation events disrupt the modulatory CH contacts, facilitating phosphorylation of the inhibitory helix and consequent GEF activation. Our findings illustrate how the opposing requirements of strong suppression of activity and rapid kinetics of activation can be achieved in multidomain systems.
Structural and energetic mechanisms of cooperative autoinhibition and activation of Vav1.,Yu B, Martins IR, Li P, Amarasinghe GK, Umetani J, Fernandez-Zapico ME, Billadeau DD, Machius M, Tomchick DR, Rosen MK Cell. 2010 Jan 22;140(2):246-56. PMID:20141838[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yu B, Martins IR, Li P, Amarasinghe GK, Umetani J, Fernandez-Zapico ME, Billadeau DD, Machius M, Tomchick DR, Rosen MK. Structural and energetic mechanisms of cooperative autoinhibition and activation of Vav1. Cell. 2010 Jan 22;140(2):246-56. PMID:20141838 doi:10.1016/j.cell.2009.12.033
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