Activated RhoA Binds to the Pleckstrin Homology (PH) Domain of PDZ-RhoGEF, a Potential Site for Autoregulation

Journal Article · Mon Jul 19 00:00:00 EDT 2010 · J. Biol. Chem.

DOI:https://doi.org/10.1074/jbc.M110.122549· OSTI ID:1002486

Chen, Zhe; Medina, Frank; Liu, Mu-ya; Thomas, Celestine; Sprang, Stephen R; Sternweis, Paul C ^[1]

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1. UTSMC

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 {center_dot} PH) domains. Unconventionally, PDZ-RhoGEF (PRG), a member of the RGS-RhoGEFs, binds tightly to both nucleotide-free and activated RhoA (RhoA {center_dot} GTP). We have characterized the interaction between PRG and activated RhoA and determined the structure of the PRG-DH {center_dot} PH-RhoA {center_dot} GTP{gamma}S (guanosine 5{prime}-O-[{gamma}-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 PRG-DH {center_dot} PH do not overlap, and a ternary complex of PRG-DH {center_dot} 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.

• Research Organization: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
• Sponsoring Organization: USDOE
• OSTI ID: 1002486
• Journal Information: J. Biol. Chem., Vol. 285, Issue (27) ; 07, 2010; ISSN 0021-9258
• Country of Publication: United States
• Language: ENGLISH

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