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GTPase mechanism of Gproteins from the 1.7-Å crystal structure of transducin α - GDP AIF−4

Nature volume 372, pages 276–279 (1994)Cite this article

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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Authors and Affiliations

  1. Department of Molecular Biophysics and Biochemistry and the Howard Hughes Medical Institute, Yale University, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, Connecticut, 06510, USA

    John Sondek, David G. Lambright, Joseph P. Noel & Paul B. Sigler

  2. Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, Illinois, 60680, USA

    Heidi E. Hamm

  3. Istituto di Fisiologia General e Chimica Biologica, Universita' di Sassari, Sassari, 07100, Italy

    Heidi E. Hamm

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  1. John Sondek
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  4. Heidi E. Hamm
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  5. Paul B. Sigler
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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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