1rqq
From Proteopedia
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'''Crystal Structure of the Insulin Receptor Kinase in Complex with the SH2 Domain of APS''' | '''Crystal Structure of the Insulin Receptor Kinase in Complex with the SH2 Domain of APS''' | ||
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[[Category: Liu, J.]] | [[Category: Liu, J.]] | ||
[[Category: Saltiel, A R.]] | [[Category: Saltiel, A R.]] | ||
| - | [[Category: | + | [[Category: Adaptor protein]] |
| - | [[Category: | + | [[Category: Protein tyrosine kinase]] |
| - | [[Category: | + | [[Category: Sh2 domain]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 07:48:10 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 04:48, 3 May 2008
Crystal Structure of the Insulin Receptor Kinase in Complex with the SH2 Domain of APS
Contents |
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 disease 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. 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 Page seeded by OCA on Sat May 3 07:48:10 2008
