Structural basis for specific binding of the gads SH3 domain to an RxxK motif-containing SLP-76 peptide: A novel mode of peptide recognition

被引：108

作者：

Liu, Q

Berry, D

Nash, P

Pawson, T

McGlade, CJ

Li, SSC ^{[1
]}

机构：

[1] Univ Western Ontario, Fac Med & Dent, Dept Biochem, London, ON N6A 5C1, Canada

[2] Hosp Sick Children, Arthur & Sonia Labatt Brain Tumor Res Ctr, Toronto, ON M5G 1X8, Canada

[3] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada

[4] Univ Toronto, Dept Med Genet & Microbiol, Toronto, ON M5S 1A8, Canada

[5] Univ Toronto, Dept Med Biophys, Toronto, ON M5S 1A8, Canada

[6] Child Hlth Res Inst, London, ON N6C 2V5, Canada

来源：

MOLECULAR CELL | 2003年 / 11卷 / 02期

关键词：

D O I：

10.1016/S1097-2765(03)00046-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The SH3 domain, which normally recognizes proline-rich sequences, has the potential to bind motifs with an RxxK consensus. To explore this novel specificity, we have determined the solution structure of the Gads T cell adaptor C-terminal SH3 domain in complex with an RSTK-containing peptide, representing its physiological binding site on the SLP-76 docking protein. The SLP-76 peptide engages four distinct binding pockets on the surface of the Gads SH3 domain and upon binding adopts a unique structure characterized by a right-handed 3(10) helix at the RSTK locus, in contrast to the left-handed polyproline type II helix formed by canonical proline-rich SH3 ligands. The structure, and supporting mutagenesis and peptide binding data, reveal a novel mode of ligand recognition by SH3 domains.

引用

页码：471 / 481

页数：11

共 47 条

[1] A high-affinity Arg-X-X-Lys SH3 binding motif confers specificity for the interaction between gads and SLP-76 in T cell signaling [J].