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Science 310 (5754): 1686-1690

Copyright © 2005 by the American Association for the Advancement of Science

Snapshot of Activated G Proteins at the Membrane: The G{alpha}q-GRK2-Gß{gamma} Complex

Valerie M. Tesmer,1,2 Takeharu Kawano,3* Aruna Shankaranarayanan,1,2* Tohru Kozasa,4 John J. G. Tesmer1,2{dagger}

Abstract: G protein–coupled receptor kinase 2 (GRK2) plays a key role in the desensitization of G protein–coupled receptor signaling by phosphorylating activated heptahelical receptors and by sequestering heterotrimeric G proteins. We report the atomic structure of GRK2 in complex with G{alpha}q and Gß{gamma}, in which the activated G{alpha} subunit of Gq is fully dissociated from Gß{gamma} and dramatically reoriented from its position in the inactive G{alpha}ß{gamma} heterotrimer. G{alpha}q forms an effector-like interaction with the GRK2 regulator of G protein signaling (RGS) homology domain that is distinct from and does not overlap with that used to bind RGS proteins such as RGS4.

1 Institute for Cellular and Molecular Biology, Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, TX 78712, USA.
2 Life Sciences Institute, Department of Pharmacology, University of Michigan, Ann Arbor, MI 48109, USA.
3 Department of Anatomy and Cell Biology, University of Illinois, Chicago, IL 60612, USA.
4 Department of Pharmacology, University of Illinois, Chicago, IL 60612, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: johntesmer{at}umich.edu

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