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Oligomerization of G Protein-Coupled Receptors:  Past, Present, and Future

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Departments of Ophthalmology, Pharmacology, and Chemistry, University of Washington, Seattle, Washington 98195, Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada M5S 2S2, and International Institute of Molecular and Cell Biology, Warsaw, PL-02109 Poland
Cite this: Biochemistry 2004, 43, 50, 15643–15656
Publication Date (Web):November 19, 2004
Copyright © 2004 American Chemical Society

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    Abstract Image

    G protein-coupled receptor (GPCR)-mediated signal transduction has been studied for more than a century. Despite the intense focus on this class of proteins, a molecular understanding of what constitutes the functional form of the receptor is still uncertain. GPCRs have traditionally been conceptualized as monomeric proteins, and this view has changed little over the years until relatively recently. Recent biochemical and biophysical studies have challenged this traditional concept, and point instead to a mechanistic view of signal transduction wherein the receptor functions as an oligomer. Cooperative interactions within such an oligomeric array may be critical for the propagation of an external signal across the cell membrane and to the G protein, and may therefore underlie the mechanistic basis of signaling.

     This work was supported in part by U.S. Public Health Service Grant EY08061 from the National Eye Institute (National Institutes of Health, Bethesda, MD), an unrestricted grant from Research to Prevent Blindness, Inc. (RPB, New York, NY), to the Department of Ophthalmology at the University of Washington, and a grant from the E. K. Bishop Foundation to K.P. This study also was supported by funds from Polish State Committee for Scientific Research (Grant 3P05F02625 to S.F.), the Canadian Institutes of Health Research (Grant MOP43990, to J.W.W.), and the Heart and Stroke Foundation of Ontario (Grant T4914, to J.W.W.). P.S.-H.P. is the recipient of a postdoctoral fellowship from the Natural Sciences and Engineering Research Council of Canada.


     To whom correspondence should be addressed:  Department of Ophthalmology, University of Washington, Box 356485, Seattle, WA 98195-6485. Phone:  (206) 543-9074. Fax:  (206) 221-6784. E-mail:  [email protected] (P.S.-H.P.) or [email protected] (K.P.).

     Department of Ophthalmology, University of Washington.


     International Institute of Molecular and Cell Biology.

     University of Toronto.

     Department of Pharmacology, University of Washington.


     Department of Chemistry, University of Washington.

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    An animated video illustrating the potential interaction between rhodopsin (ground-state, blue; photon-activated, yellow) and transducin (Gα, orange; Gβ, red; Gγ, green). GTP is represented in purple, and GDP is represented in light purple. The video is based on information obtained from atomic force microscopy and molecular modeling using information from the crystal structures of the two components (54, 100, 120) . This material is available free of charge via the Internet at

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    Your Mendeley pairing has expired. Please reconnect