GEFs: structural basis for their activation of small GTP-binding proteins

Small GTP-binding proteins of the Ras superfamily function as molecular swi tches in fundamental events such as signal transduction, cytoskeleton dynam ics and intracellular trafficking. Guanine-nucleotide-exchange factors (GEF s) positively regulate these GTP-binding proteins in response to a variety of signals. GEFs catalyze the dissociation of GDP from the inactive GTP-bin ding proteins. GTP can then bind and induce structural changes that allow i nteraction with effecters. Representative structures of four main classes o f exchange factors have been described recently and, in two cases, structur es of the GTP-binding protein-GEF complex have been solved. These structure s, together with biochemical studies, have allowed a deeper understanding o f the mechanisms of activation of Ras-like GTP-binding proteins and suggest ed how they might represent targets for therapeutic intervention.