View source for 2lct


==Solution structure of the Vav1 SH2 domain complexed with a Syk-derived doubly phosphorylated peptide==
<StructureSection load='2lct' size='340' side='right'caption='[[2lct]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2lct]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LCT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LCT FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></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=2lct FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lct OCA], [https://pdbe.org/2lct PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lct RCSB], [https://www.ebi.ac.uk/pdbsum/2lct PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lct ProSAT]</span></td></tr>
</table>
== Function ==
[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.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Activated Syk, an essential tyrosine kinase in B cell signaling, interacts with Vav guanine nucleotide exchange factors and regulates Vav activity through tyrosine phosphorylation. The Vav SH2 domain binds Syk linker B by an unusual recognition of two closely spaced Syk tyrosines: Y342 and Y346. The binding affinity is highest when both Y342 and Y346 are phosphorylated. An investigation in B cells of the dependence of Vav phosphorylation and NFAT activation on phosphorylation of Y342 and Y346 finds that cellular response levels match the relative binding affinities of the Vav1 SH2 domain for singly and doubly phosphorylated linker B peptides. This key result suggests that the uncommon recognition determinant of these two closely spaced tyrosines is a limiting factor in signaling. Interestingly, differences in affinities for binding singly and doubly phosphorylated peptides are reflected in the on rate, not the off rate. Such a control mechanism would be highly effective for regulating binding among competing Syk binding partners. The nuclear magnetic resonance (NMR) structure of Vav1 SH2 in complex with a doubly phosphorylated linker B peptide reveals diverse conformations associated with the unusual SH2 recognition of two phosphotyrosines. NMR relaxation indicates compensatory changes in loop fluctuations upon binding, with implications for nonphosphotyrosine interactions of Vav1 SH2.

Two closely spaced tyrosines regulate NFAT signaling in B cells via Syk association with Vav.,Chen CH, Martin VA, Gorenstein NM, Geahlen RL, Post CB Mol Cell Biol. 2011 Jul;31(14):2984-96. Epub 2011 May 23. PMID:21606197<ref>PMID:21606197</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2lct" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Chen C]]
[[Category: Gorenstein N]]
[[Category: Post C]]