1rqq

From Proteopedia

Crystal Structure of the Insulin Receptor Kinase in Complex with the SH2 Domain of APS

Overview

The adaptor protein APS is a substrate of the insulin receptor and couples, receptor activation with phosphorylation of Cbl to facilitate glucose, uptake. The interaction with the activated insulin receptor is mediated by, the Src homology 2 (SH2) domain of APS. Here, we present the crystal, structure of the APS SH2 domain in complex with the phosphorylated, tyrosine kinase domain of the insulin receptor. The structure reveals a, novel dimeric configuration of the APS SH2 domain, wherein the C-terminal, half of each protomer is structurally divergent from conventional, monomeric SH2 domains. The APS SH2 dimer engages two kinase molecules, with pTyr-1158 of the kinase activation loop bound in the canonical, phosphotyrosine binding pocket of the SH2 domain and a second, phosphotyrosine, pTyr-1162, coordinated by two lysine residues in beta, strand D. This structure provides a molecular visualization of one of the, initial downstream recruitment events following insulin activation of its, dimeric receptor.

Disease

Known diseases associated with this structure: Diabetes mellitus, insulin-resistant, with acanthosis nigricans OMIM:[147670], Hyperinsulinemic hypoglycemia, familial, 5 OMIM:[147670], Leprechaunism OMIM:[147670], Rabson-Mendenhall syndrome OMIM:[147670]

About this Structure

1RQQ is a Protein complex structure of sequences from Homo sapiens and Rattus norvegicus with MN and 112 as ligands. Active as Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 Full crystallographic information is available from OCA.

Reference

Structural basis for recruitment of the adaptor protein APS to the activated insulin receptor., Hu J, Liu J, Ghirlando R, Saltiel AR, Hubbard SR, Mol Cell. 2003 Dec;12(6):1379-89. PMID:14690593

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