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Crystal Structure of Src SH2 domain bound to doubly phosphorylated peptide PQpYIpYVPACrystal Structure of Src SH2 domain bound to doubly phosphorylated peptide PQpYIpYVPA
Structural highlights
FunctionSRC_RSVSA This phosphoprotein, required for both the initiation and the maintenance of neoplastic transformation, is a protein kinase that catalyzes the phosphorylation of tyrosine residues in vitro. 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 PubMedRecruitment of the Src kinase to the activated form of the platelet-derived growth factor (PDGF) receptor involves recognition of a unique sequence motif in the juxtamembrane region of the receptor by the Src homology 2 (SH2) domain of the enzyme. This motif contains two phosphotyrosine residues separated by one residue (sequence pYIpYV where pY indicates a phosphotyrosine). Here, we provide the thermodynamic and structural basis for the binding of this motif by the Src SH2 domain. We show that the second phosphorylation event increases the free energy window for specific interaction and that the physiological target is exquisitely designed for the task of recruiting specifically an SH2 domain which otherwise demonstrates very little intrinsic ability to discriminate sequences C-terminal to the first phosphorylation event. Surprisingly, we show that water plays a role in the recognition process. Structural and thermodynamic basis for the interaction of the Src SH2 domain with the activated form of the PDGF beta-receptor.,Lubman OY, Waksman G J Mol Biol. 2003 May 2;328(3):655-68. PMID:12706723[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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