3BU3

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

3BU3 の概要

• エントリーDOI: 10.2210/pdb3bu3/pdb
• 関連するPDBエントリー: 3BU5 3BU6
• 分子名称: insulin receptor subunit beta, Insulin receptor substrate 2 (3 entities in total)
• 機能のキーワード: irk, krlb, irs2, insulin receptor, substrate, alternative splicing, atp-binding, carbohydrate metabolism, cleavage on pair of basic residues, diabetes mellitus, disease mutation, glycoprotein, kinase, membrane, nucleotide-binding, phosphoprotein, polymorphism, transferase, transmembrane, tyrosine-protein kinase, transducer
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cell membrane; Single-pass type I membrane protein: P06213; Cytoplasm, cytosol: P81122
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 36749.43

構造登録者

Wu, J.,Hubbard, S.R. (登録日: 2007-12-31, 公開日: 2008-02-19, 最終更新日: 2024-10-30)

主引用文献

Wu, J.,Tseng, Y.D.,Xu, C.F.,Neubert, T.A.,White, M.F.,Hubbard, S.R.
Structural and biochemical characterization of the KRLB region in insulin receptor substrate-2.
Nat.Struct.Mol.Biol., 15:251-258, 2008

PubMed Abstract: 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.

PubMed: 18278056
DOI: 10.1038/nsmb.1388

実験手法

X-RAY DIFFRACTION (1.65 Å)