Structure of the rgRGs domain of p115RhoGEF

Zhe Chen; Clark D. Wells; Paul C. Sternweis; Stephen R. Sprang

doi:10.1038/nsb0901-805

Structure of the rgRGs domain of p115RhoGEF

Zhe Chen
, Clark D. Wells
, Paul C. Sternweis
, Stephen R. Sprang

Division of Biological and Biomedical Sciences

University of Texas Southwestern Medical Center

Research output: Contribution to journal › Article › peer-review

53 Scopus citations

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.

Original language	English
Pages (from-to)	805-809
Number of pages	5
Journal	Nature Structural Biology
Volume	8
Issue number	9
DOIs	https://doi.org/10.1038/nsb0901-805
State	Published - 2001

Funding

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.

Funder number
R01DK046371

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10.1038/nsb0901-805

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title = "Structure of the rgRGs domain of p115RhoGEF",

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 {\AA} 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.",

author = "Zhe Chen and Wells, \{Clark D.\} and Sternweis, \{Paul C.\} and Sprang, \{Stephen R.\}",

note = "Funding Information: 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.",

year = "2001",

doi = "10.1038/nsb0901-805",

language = "English",

volume = "8",

pages = "805--809",

journal = "Nature Structural Biology",

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T1 - Structure of the rgRGs domain of p115RhoGEF

AU - Chen, Zhe

AU - Wells, Clark D.

AU - Sternweis, Paul C.

AU - Sprang, Stephen R.

N1 - Funding Information: 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.

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/0034862889

U2 - 10.1038/nsb0901-805

DO - 10.1038/nsb0901-805

M3 - Article

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AN - SCOPUS:0034862889

SN - 1072-8368

VL - 8

SP - 805

EP - 809

JO - Nature Structural Biology

JF - Nature Structural Biology

IS - 9

ER -

Structure of the rgRGs domain of p115RhoGEF

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