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 inactive GDP-bound protein is turned on by a guanine nucleotide exchange factor (GEF) that catalyzes exchange of GTP for GDP, but unfortunately little is known about the mechanism of GEF action. A common mechanism for GDP/GTP exchange can be envisioned wherein GEFs activate monomeric GTPases through transient disruption of Mg2+ coordination in the nucleotide-binding pocket while stabilizing a nucleotide-free (and cation-free) conformation. After guanine nucleotide exchange, Mg2+ coordination is restored to complete the conformational switch to the active GTP-bound state. Evidence in the literature highlighting an important regulatory role for Mg2+ in the mechanism of GEF-mediated GDP/GTP exchange by monomeric GTPases is summarized.
Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA. wessling@hsph.harvard.edu
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Wessling-Resnick
D000818:Animals; D020558:GTP Phosphohydrolases / Q000737:chemistry / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors; D006150:Guanine Nucleotides / Q000378:metabolism*; D066298:In Vitro Techniques; D008274:Magnesium / Q000378:metabolism; D008954:Models, Biological; D011506:Proteins / Q000378:metabolism*
D020662:Guanine Nucleotide Exchange Factors; D006150:Guanine Nucleotides; D011506:Proteins; D020558:GTP Phosphohydrolases; D008274:Magnesium