3KZ1

Crystal Structure of the Complex of PDZ-RhoGEF DH/PH domains with GTP-gamma-S Activated RhoA

Summary for 3KZ1

• Entry DOI: 10.2210/pdb3kz1/pdb
• Related: 1A2B 1TXD 1X86 1XCG
• Descriptor: Rho guanine nucleotide exchange factor 11, Transforming protein RhoA, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: regulation of rhoa gtpase, rhogef, dh, ph, rho, gtpase activation, guanine-nucleotide releasing factor, membrane, cytoskeleton, gtp-binding, magnesium, nucleotide-binding, prenylation, proto-oncogene, signaling protein
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: O15085; Cell membrane; Lipid-anchor; Cytoplasmic side: P61586
• Total number of polymer chains: 4
• Total formula weight: 131312.79

Authors

Chen, Z.,Sternweis, P.C.,Sprang, S.R. (deposition date: 2009-12-07, release date: 2010-04-28, Last modification date: 2023-09-06)

Primary citation

Chen, Z.,Medina, F.,Liu, M.Y.,Thomas, C.,Sprang, S.R.,Sternweis, P.C.
Activated RhoA binds to the pleckstrin homology (PH) domain of PDZ-RhoGEF, a potential site for autoregulation.
J.Biol.Chem., 285:21070-21081, 2010

PubMed 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.GTPgammaS (guanosine 5'-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.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.

PubMed: 20430886
DOI: 10.1074/jbc.M110.122549

Experimental method

X-RAY DIFFRACTION (2.7 Å)