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3bu6

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{{STRUCTURE_3bu6| PDB=3bu6 | SCENE= }}
{{STRUCTURE_3bu6| PDB=3bu6 | SCENE= }}
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'''Crystal structure of the insulin receptor kinase in complex with IRS2 KRLB phosphopeptide'''
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===Crystal structure of the insulin receptor kinase in complex with IRS2 KRLB phosphopeptide===
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==Overview==
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Insulin receptor substrates 1 and 2 (IRS1 and -2) are crucial adaptor proteins in mediating the metabolic and mitogenic effects of insulin and insulin-like growth factor 1. These proteins consist of a pleckstrin homology domain, a phosphotyrosine binding domain and a C-terminal region containing numerous sites of tyrosine, serine and threonine phosphorylation. Previous yeast two-hybrid studies identified a region unique to IRS2, termed the kinase regulatory-loop binding (KRLB) region, which interacts with the tyrosine kinase domain of the insulin receptor. Here we present the crystal structure of the insulin receptor kinase in complex with a 15-residue peptide from the KRLB region. In the structure, this segment of IRS2 is bound in the kinase active site with Tyr628 positioned for phosphorylation. Although Tyr628 was phosphorylated by the insulin receptor, its catalytic turnover was poor, resulting in kinase inhibition. Our studies indicate that the KRLB region functions to limit tyrosine phosphorylation of IRS2.
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==Disease==
==Disease==
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[[Category: Transmembrane]]
[[Category: Transmembrane]]
[[Category: Tyrosine-protein kinase]]
[[Category: Tyrosine-protein kinase]]
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Revision as of 04:28, 29 July 2008

Image:3bu6.png

Template:STRUCTURE 3bu6

Contents

Crystal structure of the insulin receptor kinase in complex with IRS2 KRLB phosphopeptide

Template:ABSTRACT PUBMED 18278056

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

3BU6 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural and biochemical characterization of the KRLB region in insulin receptor substrate-2., Wu J, Tseng YD, Xu CF, Neubert TA, White MF, Hubbard SR, Nat Struct Mol Biol. 2008 Mar;15(3):251-8. Epub 2008 Feb 17. PMID:18278056

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