@article{a6f1ac40ac4c4d62934667209867afc2,
title = "Activated RhoA binds to the Pleckstrin Homology (PH) domain of PDZ-RhoGEF, a potential site for autoregulation",
abstract = "Guanine nucleotide exchange factors (GEFs) catalyze exchange of GDP for GTP by stabilizing the nucleotide-free state of the small GTPases through their Dbl homology/pleckstrin homology (DH·PH) domains. Unconventionally, PDZ-RhoGEF (PRG), a member of the RGS-RhoGEFs, binds tightly to both nucleotide-free and activated RhoA (RhoA·GTP). We have characterized the interaction between PRG and activated RhoA and determined the structure of the PRG-DH·PH-RhoA·GTPγS (guanosine 5′-O-[γ-thio] triphosphate) complex. The interface bears striking similarity to a GTPase-effector interface and involves the switch regions in RhoA and a hydrophobic patch in PRG-PH that is conserved among all Lbc RhoGEFs. The two surfaces that bind activated and nucleotide-free RhoA on PRGD-H ·PH do not overlap, and a ternary complex of PRG-DH·PH bound to both forms of RhoA can be isolated by size-exclusion chromatography. This novel interaction between activated RhoA and PH could play a key role in regulation of RhoGEF activity in vivo.",
author = "Zhe Chen and Frank Medina and Liu, \{Mu Ya\} and Celestine Thomas and Sprang, \{Stephen R.\} and Sternweis, \{Paul C.\}",
year = "2010",
month = jul,
day = "2",
doi = "10.1074/jbc.M110.122549",
language = "English",
volume = "285",
pages = "21070--21081",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "27",
}