6BC0

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

Summary for 6BC0

• Entry DOI: 10.2210/pdb6bc0/pdb
• Descriptor: Rho guanine nucleotide exchange factor 28, Transforming protein RhoA, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: rho gtpase guanine nucleotide exchange factors rhogef pleckstrin homology ph domain, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 38962.63

Authors

Chen, Z.,Sternweis, P.C. (deposition date: 2017-10-20, release date: 2017-12-13, Last modification date: 2024-03-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.198 Å)