2AUH

Crystal structure of the Grb14 BPS region in complex with the insulin receptor tyrosine kinase

2AUH の概要

• エントリーDOI: 10.2210/pdb2auh/pdb
• 分子名称: Insulin receptor, Growth factor receptor-bound protein 14, CALCIUM ION (3 entities in total)
• 機能のキーワード: tyrosine kinase, bps region, 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: Q14449
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 41439.91

構造登録者

Depetris, R.S.,Hu, J.,Gimpelevich, I.,Holt, L.J.,Daly, R.J.,Hubbard, S.R. (登録日: 2005-08-27, 公開日: 2005-11-01, 最終更新日: 2024-11-20)

主引用文献

Depetris, R.S.,Hu, J.,Gimpelevich, I.,Holt, L.J.,Daly, R.J.,Hubbard, S.R.
Structural basis for inhibition of the insulin receptor by the adaptor protein grb14.
Mol.Cell, 20:325-333, 2005

PubMed Abstract: Grb14, a member of the Grb7 adaptor protein family, possesses a pleckstrin homology (PH) domain, a C-terminal Src homology-2 (SH2) domain, and an intervening stretch of approximately 45 residues known as the BPS region, which is unique to this adaptor family. Previous studies have demonstrated that Grb14 is a tissue-specific negative regulator of insulin receptor signaling and that inhibition is mediated by the BPS region. We have determined the crystal structure of the Grb14 BPS region in complex with the tyrosine kinase domain of the insulin receptor. The structure reveals that the N-terminal portion of the BPS region binds as a pseudosubstrate inhibitor in the substrate peptide binding groove of the kinase. Together with the crystal structure of the SH2 domain, we present a model for the interaction of Grb14 with the insulin receptor, which indicates how Grb14 functions as a selective protein inhibitor of insulin signaling.

PubMed: 16246733
DOI: 10.1016/j.molcel.2005.09.001

実験手法

X-RAY DIFFRACTION (3.2 Å)