Abstract
ALUMINIUM fluoride (A1F−4) activates members of the hetero-trimeric G-protein (Gαβγ) family1,2 by binding to inactive Gα·GDP near the site occupied by the γ-phosphate in Gα·GTP (ref. 3). Here we describe the crystal structure of transducin a o GDP acti-vated with aluminium fluoride (Gtα·GDP·A1F−4·H·O) at 1.7 Å, a resolution sufficient to establish the coordination geometry of the bound aluminium fluoride as well as the extensive network of direct and water-mediated interactions that stabilize it. These observations are derived from three independent representations in the asymmetric unit, eliminating any chance of drawing conclu-sions based on stereochemistry imposed by crystal packing. Surprisingly, aluminium fluoride activates Gα·GDP by binding with a geometry resembling a pentavalent intermediate for GTP hydrolysis. The stabilizing interactions involve not only residues that interact with the y-phosphate in Gtα·GTPγS, but also conserved residues essential for GTPase activity. Thus the Gtα·GDP·AIF−4·H2O structure provides new insight into the mechanism of GTP hydrolysis.
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Sondek, J., Lambright, D., Noel, J. et al. GTPase mechanism of Gproteins from the 1.7-Å crystal structure of transducin α - GDP AIF−4. Nature 372, 276–279 (1994). https://doi.org/10.1038/372276a0
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DOI: https://doi.org/10.1038/372276a0
