1RQQ

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

1RQQ の概要

• エントリーDOI: 10.2210/pdb1rqq/pdb
• 分子名称: Insulin receptor, adaptor protein APS, BISUBSTRATE INHIBITOR, ... (6 entities in total)
• 機能のキーワード: protein tyrosine kinase, adaptor protein, sh2 domain, transferase-signaling protein complex, transferase/signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P06213; Cytoplasm: Q9Z200
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 100999.71

構造登録者

Hu, J.,Liu, J.,Ghirlando, R.,Saltiel, A.R.,Hubbard, S.R. (登録日: 2003-12-06, 公開日: 2003-12-30, 最終更新日: 2024-10-09)

主引用文献

Hu, J.,Liu, J.,Ghirlando, R.,Saltiel, A.R.,Hubbard, S.R.
Structural basis for recruitment of the adaptor protein APS to the activated insulin receptor.
Mol.Cell, 12:1379-1389, 2003

PubMed Abstract: 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.

PubMed: 14690593
DOI: 10.1016/S1097-2765(03)00487-8

実験手法

X-RAY DIFFRACTION (2.6 Å)