Structural Elements, Mechanism, and Evolutionary Convergence of Rho Protein-Guanine Nucleotide Exchange Factor Complexes

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• 作者：Jon W. Erickson and Richard A. Cerione
• 刊名：Biochemistry
• 出版年：2004
• 出版时间：February 3, 2004
• 年：2004
• 卷：43
• 期：4
• 页码：837 - 842
• 全文大小：160K
• 年卷期：v.43,no.4(February 3, 2004)
• ISSN：1520-4995

文摘

Rho GTPases act as key regulators of cellular biochemistry by determining the timing, direction,and amplitude of signal transduction in a number of important pathways. The rate of activation of aGTPase-controlled reaction is limited by the rate of GTP binding to the Rho protein, and this, in turn,depends on the rate that GDP dissociates from the GTPase. The latter is controlled by the action ofguanine nucleotide exchange factors (GEFs) that catalyze GDP-GTP exchange by increasing the rate ofGDP dissociation. Here, the recently reported structural information for Rho GTPase-GEF complexesand the molecular basis for the specificity of their interactions are discussed. Underscoring the importanceof regulating the Rho GTPase activation pathway, genetically unrelated proteins have evolved whichcomplement or mimic the Dbl homology-Pleckstrin homology (DH-PH) domain-containing family ofproteins in their ability to catalyze GDP-GTP exchange. In particular, the structure of the mammalianCdc42 protein bound to the SopE protein from Salmonella typhimurium illustrates how two unrelatedprotein folds are able to carry out guanine nucleotide exchange by a remarkably similar mechanism. Itwill be interesting to see if this conservation of mechanism extends to a newly recognized class of GEFsrelated to the DOCK180 family.