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p115RhoGEF的rgRGS结构域的结构

Structure of the rgRGS domain of p115RhoGEF.

作者信息

Chen Z, Wells C D, Sternweis P C, Sprang S R

机构信息

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

出版信息

Nat Struct Biol. 2001 Sep;8(9):805-9. doi: 10.1038/nsb0901-805.

DOI:10.1038/nsb0901-805
PMID:11524686
Abstract

p115RhoGEF, a guanine nucleotide exchange factor for Rho GTPase, is also a GTPase activating protein (GAP) for G(12) and G(13) heterotrimeric G alpha 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 A 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 G alpha(13) that are analogous to those in complexes of RGS proteins with their G alpha substrates.

摘要

p115RhoGEF是一种Rho GTP酶的鸟嘌呤核苷酸交换因子,也是G(12)和G(13)异三聚体Gα亚基的GTP酶激活蛋白(GAP)。在其N端附近,p115RhoGEF包含一个与RGS(G蛋白信号调节剂)结构域具有远缘序列同源性的结构域(rgRGS)。rgRGS结构域对于p115RhoGEF的GAP活性是必需的,但并不充分。rgRGS结构域1.9埃分辨率的晶体结构显示出与RGS结构域的结构相似性,但具有一个C端延伸,该延伸折叠成一层螺旋,堆积在该结构域的疏水核心上。诱变实验表明,rgRGS可能与Gα(13)形成类似于RGS蛋白与其Gα底物复合物中的相互作用。

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