3bu5

File:3bu5.jpg

spinqualitylabelsall models 3bu5, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal structure of the insulin receptor kinase in complex with IRS2 KRLB peptide and ATP

OverviewOverview

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.

About this StructureAbout this Structure

3BU5 is a Protein complex structure of sequences from Homo sapiens with and as ligands. Active as Receptor protein-tyrosine kinase, with EC number 2.7.10.1 Known structural/functional Sites: and . Full crystallographic information is available from OCA.

ReferenceReference

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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