PDBsum entry 2mc1

Signaling protein/protein binding

PDB id: 2mc1

Contents

Protein chains

107 a.a.

13 a.a.

PDB id:

2mc1

Name:

Signaling protein/protein binding

Title:

Solution structure of the vav1 sh2 domain complexed with a syk-derived singly phosphorylated peptide

Structure:

Proto-oncogene vav. Chain: a. Fragment: sh2 domain (unp residues 664-767). Engineered: yes. Tyrosine-protein kinase syk. Chain: b. Fragment: unp residues 338-350. Synonym: spleen tyrosine kinase. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: vav1, vav. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Mus musculus. Mouse.

NMR struc:

20 models

Authors:

C.Chen,D.Piraner,N.M.Gorenstein,R.L.Geahlen,C.B.Post

Key ref:

C.H.Chen et al. (2013). Differential recognition of syk-binding sites by each of the two phosphotyrosine-binding pockets of the Vav SH2 domain. Biopolymers, 99, 897-907. PubMed id: 23955592 DOI: 10.1002/bip.22371

Date:

13-Aug-13 Release date: 28-Aug-13

Protein chain

P15498  (VAV_HUMAN) -  Proto-oncogene vav from Homo sapiens

Seq: 845 a.a.

Struc: 107 a.a.*

Protein chain

P48025  (KSYK_MOUSE) -  Tyrosine-protein kinase SYK from Mus musculus

Seq: 629 a.a.

Struc: 13 a.a.

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chain B: E.C.2.7.10.2 - non-specific protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1002/bip.22371

Biopolymers 99:897-907 (2013)

PubMed id: 23955592

Differential recognition of syk-binding sites by each of the two phosphotyrosine-binding pockets of the Vav SH2 domain.

C.H.Chen, D.Piraner, N.M.Gorenstein, R.L.Geahlen, C.Beth Post.

ABSTRACT

The association of spleen tyrosine kinase (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 β-sheet. 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 (SykLB-YpY) modeling the singly phosphorylated-Y346 form of Syk with unphosphorylated Y342. The nuclear magnetic resonance (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 SykLB-YpY 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 protein-protein interactions in cellular signaling. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 897-907, 2013.