4YON

P-Rex1:Rac1 complex

4YON の概要

• エントリーDOI: 10.2210/pdb4yon/pdb
• 分子名称: Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 protein, Ras-related C3 botulinum toxin substrate 1 (3 entities in total)
• 機能のキーワード: protein binding
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 65538.19

構造登録者

Lucato, C.M.,Whisstock, J.C.,Ellisdon, A.M. (登録日: 2015-03-11, 公開日: 2015-07-01, 最終更新日: 2023-09-27)

主引用文献

Lucato, C.M.,Halls, M.L.,Ooms, L.M.,Liu, H.J.,Mitchell, C.A.,Whisstock, J.C.,Ellisdon, A.M.
The Phosphatidylinositol (3,4,5)-Trisphosphate-dependent Rac Exchanger 1Ras-related C3 Botulinum Toxin Substrate 1 (P-Rex1Rac1) Complex Reveals the Basis of Rac1 Activation in Breast Cancer Cells.
J.Biol.Chem., 290:20827-20840, 2015

PubMed Abstract: The P-Rex (phosphatidylinositol (3,4,5)-trisphosphate (PIP3)-dependent Rac exchanger) family (P-Rex1 and P-Rex2) of the Rho guanine nucleotide exchange factors (Rho GEFs) activate Rac GTPases to regulate cell migration, invasion, and metastasis in several human cancers. The family is unique among Rho GEFs, as their activity is regulated by the synergistic binding of PIP3 and Gβγ at the plasma membrane. However, the molecular mechanism of this family of multi-domain proteins remains unclear. We report the 1.95 Å crystal structure of the catalytic P-Rex1 DH-PH tandem domain in complex with its cognate GTPase, Rac1 (Ras-related C3 botulinum toxin substrate-1). Mutations in the P-Rex1·Rac1 interface revealed a critical role for this complex in signaling downstream of receptor tyrosine kinases and G protein-coupled receptors. The structural data indicated that the PIP3/Gβγ binding sites are on the opposite surface and markedly removed from the Rac1 interface, supporting a model whereby P-Rex1 binding to PIP3 and/or Gβγ releases inhibitory C-terminal domains to expose the Rac1 binding site.

PubMed: 26112412
DOI: 10.1074/jbc.M115.660456

実験手法

X-RAY DIFFRACTION (1.95 Å)