Structure of small G proteins and their regulators.

TLDR

Small G proteins are a diverse family of regulatory GTPases, with over 100 members such as Ras, Rho, Rab, Rac, Sar/Arf, and Ran, that share a conserved G domain and mediate processes from gene expression to vesicular transport. This review surveys the structural features of the G domain and examines the mechanisms by which small G proteins execute their signaling functions. The authors describe key regulators—including GAPs, GDIs, and GEFs—that modulate GTP hydrolysis, GDP binding, and nucleotide exchange, as well as interactions with downstream effectors.

Abstract

In recent years small G proteins have become an intensively studied group of regulatory GTP hydrolases involved in cell signaling. More than 100 small G proteins have been identified in eucaryotes from protozoan to human. The small G protein superfamily includes Ras, Rho Rab, Rac, Sarl/Arf and Ran homologs, which take part in numerous and diverse cellular processes, such as gene expression, cytoskeleton reorganization, microtubule organization, and vesicular and nuclear transport. These proteins share a common structural core, described as the G domain, and significant sequence similarity. In this paper we review the available data on G domain structure, together with a detailed analysis of the mechanism of action. We also present small G protein regulators: GTPase activating proteins that bind to a catalytic G domain and increase its low intrinsic hydrolase activity, GTPase dissociation inhibitors that stabilize the GDP-bound, inactive state of G proteins, and guanine nucleotide exchange factors that accelerate nucleotide exchange in response to cellular signals. Additionally, in this paper we describe some aspects of small G protein interactions with down-stream effectors.