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Letter
Nature Structural Biology  8, 805 - 809 (2001)
doi:10.1038/nsb0901-805

Structure of the rgRGS domain of p115RhoGEF

Zhe Chen1, Clark D. Wells2, Paul C. Sternweis2 & Stephen R. Sprang1, 3

1  Department of Biochemistry, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, Texas 75390-9050, USA.

2  Department of Pharmacology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, Texas 75390-9050, USA.

3  The Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, Texas 75390-9050, USA.

Correspondence should be addressed to Stephen R. Sprang stephen.sprang@utsouthwestern.edu
p115RhoGEF, a guanine nucleotide exchange factor for Rho GTPase, is also a GTPase activating protein (GAP) for G12 and G13 heterotrimeric Galpha subunits. Near its N-terminus, p115RhoGEF contains a domain (rgRGS) with remote sequence identity to RGS (regulators of G protein signaling) domains. The rgRGS domain is necessary but not sufficient for the GAP activity of p115RhoGEF. The 1.9 Å resolution crystal structure of the rgRGS domain shows structural similarity to RGS domains but possesses a C-terminal extension that folds into a layer of helices that pack against the hydrophobic core of the domain. Mutagenesis experiments show that rgRGS may form interactions with Galpha13 that are analogous to those in complexes of RGS proteins with their Galpha substrates.


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Nature Structural & Molecular Biology
ISSN: 1545-9993
EISSN: 1545-9985
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