Structure of the p115RhoGEF rgRGS domain-Gα13/i1 chimera complex suggests convergent evolution of a GTPase activator

Zhe Chen, William D. Singer, Paul C. Sternweis, Stephen R. Sprang

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Abstract

p115RHoGEF, a guanine nucleotide exchange factor (GEF) for Rho GTPase, is also a GTPase-activating protein (GAP) for G12 and G13 heterotrimeric Gα subunits. The GAP function of p115RhoGEF resides within the N-terminal region of p115RhoGEF (the rgRGS domain), which includes a module that is structurally similar to RGS (regulators of G-protein signaling) domains. We present here the crystal structure of the rgRGS domain of p115RhoGEF in complex with a chimera of Gα13 and Gαi1. Two distinct surfaces of rgRGS interact with Gα. The N-terminal βN-αN hairpin of rgRGS, rather than its RGS module, forms intimate contacts with the catalytic site of Gα. The interface between the RGS module of rgRGS and Gα is similar to that of a Gα-effector complex, suggesting a role for the rgRGS domain in the stimulation of the GEF activity of p115RhoGEF by Gα13.

Original languageEnglish (US)
Pages (from-to)191-197
Number of pages7
JournalNature Structural and Molecular Biology
Volume12
Issue number2
DOIs
StatePublished - Feb 20 2005

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ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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