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GEF‐mediated GDP/GTP exchange by monomeric GTPases: A regulatory role for Mg 2+ ?
Author(s) -
Pan Julie Y.,
WesslingResnick Marianne
Publication year - 1998
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/(sici)1521-1878(199806)20:6<516::aid-bies11>3.0.co;2-3
Subject(s) - guanine nucleotide exchange factor , gtpase , gtp' , nucleotide , guanine , guanosine diphosphate , gtp binding protein regulators , chemistry , microbiology and biotechnology , biochemistry , biophysics , g protein , biology , signal transduction , gene , enzyme
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 Mg 2+ coordination in the nucleotide‐binding pocket while stabilizing a nucleotide‐free (and cation‐free) conformation. After guanine nucleotide exchange, Mg 2+ coordination is restored to complete the conformational switch to the active GTP‐bound state. Evidence in the literature highlighting an important regulatory role for Mg 2+ in the mechanism of GEF‐mediated GDP/GTP exchange by monomeric GTPases is summarized. BioEssays 20 :516–521, 1998. © 1998 John Wiley & Sons, Inc.