SPring-8, the large synchrotron radiation facility

Date : 15 : 00-16 : 30   15 June (Tue.), 2010

Place : Kamitsubo Hall

Speaker : Tomonori Kaneko

Language : Japanese

Affiliate : Department of Biochemistry, The University of Western Ontario

Title : Structural Determinants of SH2 Domain Specificity

Abstract :
Cellular functions require specific protein-protein interactions that are often mediated by modular domains. The human genome encodes 120 Src homology 2 (SH2) domains, which mediate protein-protein interactions by binding to proteins with diverse phosphotyrosine (pTyr)-containing sequences. The structure of the SH2 domain of BRDG1, which exhibits unconventional specificity, in complex with a ligand peptide revealed a new binding pocket on the surface. From structural comparison with other SH2 domains, we found that the pocket was present in most SH2 domain but permanently blocked by a loop residue. Analysis of 63 SH2 domain structures (BRDG1 and 62 others in the Protein Data Bank) suggested that the SH2 domains contain three binding pockets, which exhibit selectivity for the three positions after the pTyr in a peptide, and that SH2 domain loops defined the accessibility and shape of these pockets.

Organizer : Takashi Kumasaka
PHS : 3475
E-mail : kumasaka@spring8.or.jp