2mc1 | pdb_00002mc1

Solution structure of the Vav1 SH2 domain complexed with a Syk-derived singly phosphorylated peptide

spinqualitylabelsall models 2mc1 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2mc1 is a 2 chain structure with sequence from Homo sapiens and Mus musculus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR, 20 models Ligands: PTR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function VAV_HUMAN Couples tyrosine kinase signals with the activation of the Rho/Rac GTPases, thus leading to cell differentiation and/or proliferation. Publication Abstract from PubMed The association of Syk, a central tyrosine kinase in B cell signaling, with Vav SH2 domain is controlled by phosphorylation of two closely spaced tyrosines in Syk linker B: Y342 and Y346. Previous studies established both singly phosphorylated and doubly phosphorylated forms play a role in signaling. The structure of the doubly phosphorylated form identified a new recognition of phosphotyrosine whereby two phosphotyrosines bind simultaneously to the Vav SH2 domain, one in the canonical pTyr pocket and one in the specificity pocket on the opposite side of the central betasheet. It is unknown if the specificity pocket can bind phosphotyrosine independent of phosphotyrosine binding the pTyr pocket. To address this gap in knowledge, we determined the structure of the complex between Vav1 SH2 and a peptide (SykLBYpY) modeling the singly phosphorylatedY346 form of Syk with unphosphorylated Y342. The NMR data conclusively establish that recognition of phosphotyrosine is swapped between the two pockets; phosphorylated pY346 binds the specificity pocket of Vav1 SH2, and unphosphorylated Y342 occupies what is normally the pTyr binding pocket. Nearly identical changes in chemical shifts occurred upon binding all three forms of singly and doubly phosphorylated peptides; however somewhat smaller shift perturbations for SykLBYpY from residues in regions of high internal mobility suggest that internal motions are coupled to binding affinity. The differential recognition that includes this swapped binding of phosphotyrosine to the specificity pocket of Vav SH2 increases the repertoire of possible phosphotyrosine binding by SH2 domains in regulating proteinprotein interactions in cellular signaling. Differential recognition of Syk-binding sites by each of the two phosphotyrosine-binding pockets of the Vav SH2 domain.,Chen CH, Piraner D, Gorenstein NM, Geahlen RL, Post CB Biopolymers. 2013 Aug 17. doi: 10.1002/bip.22371. PMID:23955592 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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