Trimeric G Proteins: Surprise Witness Tells a Tale

摘要

Like key witnesses in a detective story, protein crystal structures can surprise, intrigue, mislead, or instruct us—and often do all four at once. On page 954 of this issue, Mixon et al. (1) serve up an intriguing surprise: Crystals of the guanosinediphosphate (GDP) form of a_(il), a G protein a subunit that mediates hormonal inhibition of adenylyl cy-clase, reveal Galpha monomers linked, head-to-tail, in endless polymers. I suspect that the inference that similar Galpha polymers exist and functionin vivo is a red herring. Instead, at least to this armchair sleuth, this polymer and other clues hint at a solution to a fascinating molecular puzzle at the heart of G protein signaling: How do receptors, in combination with Gbetagamma, trigger GDP release and G protein activation?