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Structure of the rgRGS domain of p115RhoGEF

Nature Structural Biology volume 8, pages 805–809 (2001)Cite this article

Abstract

p115RhoGEF, a guanine nucleotide exchange factor for Rho GTPase, is also a GTPase activating protein (GAP) for G12 and G13 heterotrimeric Gα 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 Gα13 that are analogous to those in complexes of RGS proteins with their Gα substrates.

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Figure 1: Structure of the rgRGS domain of p115RhoGEF.
Figure 2: Structural comparison of RGS and rgRGS domains.
Figure 3: A model of the rgRGS–Gα13 complex.
Figure 4: GAP activity of p115RhoGEF rgRGS domain mutants towards Gα13.

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Acknowledgements

We thank A. Loew and T. Xiao for their assistance with data collection and MAD data analysis in addition to their guidance in structure refinement; S. Raghunathan, X. Du and K. Ihara for useful discussions; S. Gutowski for excellent technical assistance with GAP assays; and the staff of MacCHESS and ALS. This work is supported by NIH grants to S.R.S, P.C.S and C.D.W, and Welch Foundation grants to S.R.S and P.C.S.

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Authors and Affiliations

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

    Zhe Chen & Stephen R. Sprang

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

    Clark D. Wells & Paul C. Sternweis

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

    Stephen R. Sprang

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Correspondence to Stephen R. Sprang.

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Chen, Z., Wells, C., Sternweis, P. et al. Structure of the rgRGS domain of p115RhoGEF. Nat Struct Mol Biol 8, 805–809 (2001). https://doi.org/10.1038/nsb0901-805

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