GEF-MEDIATED GDP GTP EXCHANGE BY MONOMERIC GTPASES - A REGULATORY ROLE FOR MG2+/

GTPases share highly conserved guanine nucleotide-binding domains and fulfill diverse functions through a common molecular switch. An inacti ve GDP-bound protein is turned on by a guanine nucleotide exchange fac tor (GEF) that catalyzes exchange of GTP for GDP, but unfortunately li ttle is known about the mechanism of GEF action. A common mechanism fo r GDP/GTP exchange can be envisioned wherein GEFs activate monomeric G TPases through transient disruption of Mg2+ coordination in the nucleo tide-binding pocket while stabilizing a nucleotide-free (and cation-fr ee) conformation. After guanine nucleotide exchange, Mg2+ coordination is restored to complete the conformational switch to the active GTP-b ound state. Evidence in the literature highlighting an important regul atory role for Mg2+ in the mechanism of GEF-mediated GDP/GTP exchange by monomeric GTPases is summarized. (C) 1998 John Wiley & Sons, Inc.