6BC1

A Complex between PH Domain of p190RhoGEF and Activated Rac1 Bound to a GTP Analog

6BC1 の概要

• エントリーDOI: 10.2210/pdb6bc1/pdb
• 分子名称: Ras-related C3 botulinum toxin substrate 1, Rho guanine nucleotide exchange factor 28, 5'-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: rho gtpase guanine nucleotide exchange factors rhogef pleckstrin homology ph domain, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 77204.57

構造登録者

Chen, Z.,Sternweis, P.C. (登録日: 2017-10-20, 公開日: 2017-12-13, 最終更新日: 2024-03-13)

主引用文献

Dada, O.,Gutowski, S.,Brautigam, C.A.,Chen, Z.,Sternweis, P.C.
Direct regulation of p190RhoGEF by activated Rho and Rac GTPases.
J. Struct. Biol., 202:13-24, 2018

PubMed Abstract: Rho family GTPases regulate a wide range of cellular processes. This includes cellular dynamics where three subfamilies, Rho, Rac, and Cdc42, are known to regulate cell shape and migration though coordinate action. Activation of Rho proteins largely depends on Rho Guanine nucleotide Exchange Factors (RhoGEFs) through a catalytic Dbl homology (DH) domain linked to a pleckstrin homology (PH) domain that subserves various functions. The PH domains from Lbc RhoGEFs, which specifically activate RhoA, have been shown to bind to activated RhoA. Here, p190RhoGEF is shown to also bind Rac1·GTP. Crystal structures reveal that activated Rac1 and RhoA use their effector-binding surfaces to associate with the same hydrophobic surface on the PH domain. Both activated RhoA and Rac1 can stimulate exchange of nucleotide on RhoA by localization of p190RhoGEF to its substrate, RhoA·GDP, in vitro. The binding of activated RhoA provides a mechanism for positive feedback regulation as previously proposed for the family of Lbc RhoGEFs. In contrast, the novel interaction between activated Rac1 and p190RhoGEF reveals a potential mechanism for cross-talk regulation where Rac can directly effect stimulation of RhoA. The greater capacity of Rac1 to stimulate p190RhoGEF among the Lbc RhoGEFs suggests functional specialization.

PubMed: 29196061
DOI: 10.1016/j.jsb.2017.11.014

実験手法

X-RAY DIFFRACTION (2.9 Å)