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PMID: 20538466 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Oligomeric forms of G protein-coupled receptors (GPCRs).

Trends in biochemical sciences ·Vol. 35 ·No. 11 ·2010-11-00 ·Pages 595-600

Palczewski K

Abstract

Oligomerization is a general characteristic of cell membrane receptors that is shared by G protein-coupled receptors (GPCRs) together with their G protein partners. Recent studies of these complexes, both in vivo and in purified reconstituted forms, unequivocally support this contention for GPCRs, perhaps with only rare exceptions. As evidence has evolved from experimental cell lines to more relevant in vivo studies and from indirect biophysical approaches to well defined isolated complexes of dimeric receptors alone and complexed with G proteins, there is an expectation that the structural basis of oligomerization and the functional consequences for membrane signaling will be elucidated. Oligomerization of cell membrane receptors is fully supported by both thermodynamic calculations and the selectivity and duration of signaling required to reach targets located in various cellular compartments.

MeSH Terms
Animals GTP-Binding Proteins/metabolism Humans Protein Binding Protein Multimerization Receptors, G-Protein-Coupled/chemistry,metabolism Signal Transduction Thermodynamics
Chemicals
Receptors, G-Protein-Coupled GTP-Binding Proteins
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Palczewski Krzysztof
Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106-4965, USA. kxp65@case.edu
References (51)
51 references, click to expand
  1. Rhodopsin self-associates in asolectin liposomes.
    Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3060-5 PMID: 16492772
  2. Common sense about taste: from mammals to insects.
    Cell. 2009 Oct 16;139(2):234-44 PMID: 19837029
  3. Responses of retinal rods to single photons.
    J Physiol. 1979 Mar;288:613-34 PMID: 112243
  4. The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist.
    Science. 2008 Nov 21;322(5905):1211-7 PMID: 18832607
  5. Heterodimerization of dopamine receptors: new insights into functional and therapeutic significance.
    Parkinsonism Relat Disord. 2009 Dec;15 Suppl 4:S2-7 PMID: 20123551
  6. A concept for G protein activation by G protein-coupled receptor dimers: the transducin/rhodopsin interface.
    Photochem Photobiol Sci. 2004 Jun;3(6):628-38 PMID: 15170495
  7. Increasingly accurate dynamic molecular models of G-protein coupled receptor oligomers: Panacea or Pandora's box for novel drug discovery?
    Life Sci. 2010 Apr 10;86(15-16):590-7 PMID: 19465029
  8. Viral hijacking of human receptors through heterodimerization.
    Biochem Biophys Res Commun. 2008 Dec 5;377(1):93-7 PMID: 18823943
  9. Imaging nanometer domains of beta-adrenergic receptor complexes on the surface of cardiac myocytes.
    Nat Chem Biol. 2005 Sep;1(4):196-202 PMID: 16408035
  10. Phosphorylation of non-bleached rhodopsin in intact retinas and living frogs.
    J Biol Chem. 1996 Aug 16;271(33):19826-30 PMID: 8702691
  11. Fluorescent and bioluminescent protein-fragment complementation assays in the study of G protein-coupled receptor oligomerization and signaling.
    Mol Pharmacol. 2009 Apr;75(4):733-9 PMID: 19141658
  12. The supramolecular structure of the GPCR rhodopsin in solution and native disc membranes.
    Mol Membr Biol. 2004 Nov-Dec;21(6):435-46 PMID: 15764373
  13. Requirements and ontology for a G protein-coupled receptor oligomerization knowledge base.
    BMC Bioinformatics. 2007 May 30;8:177 PMID: 17537266
  14. Organization of the G protein-coupled receptors rhodopsin and opsin in native membranes.
    J Biol Chem. 2003 Jun 13;278(24):21655-21662 PMID: 12663652
  15. Role of heteromer formation in GABAB receptor function.
    Science. 1999 Jan 1;283(5398):74-7 PMID: 9872744
  16. Formation and dissociation of M1 muscarinic receptor dimers seen by total internal reflection fluorescence imaging of single molecules.
    Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2693-8 PMID: 20133736
  17. Lateral diffusion of rhodopsin in photoreceptor membrane: a reappraisal.
    Mol Vis. 2009 Aug 28;15:1717-29 PMID: 19727341
  18. Vertebrate membrane proteins: structure, function, and insights from biophysical approaches.
    Pharmacol Rev. 2008 Mar;60(1):43-78 PMID: 18321962
  19. Rhodopsin signaling and organization in heterozygote rhodopsin knockout mice.
    J Biol Chem. 2004 Nov 12;279(46):48189-96 PMID: 15337746
  20. Crystal structure of a photoactivated deprotonated intermediate of rhodopsin.
    Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16123-8 PMID: 17060607
  21. G proteins: transducers of receptor-generated signals.
    Annu Rev Biochem. 1987;56:615-49 PMID: 3113327
  22. Isolation and functional characterization of a stable complex between photoactivated rhodopsin and the G protein, transducin.
    FASEB J. 2009 Feb;23(2):371-81 PMID: 18827025
  23. Efficient coupling of transducin to monomeric rhodopsin in a phospholipid bilayer.
    J Biol Chem. 2008 Feb 15;283(7):4387-94 PMID: 18033822
  24. Crystal structure of rhodopsin: A G protein-coupled receptor.
    Science. 2000 Aug 4;289(5480):739-45 PMID: 10926528
  25. Oligomerization of G-protein-coupled receptors shown by selective co-immunoprecipitation.
    J Biol Chem. 2002 May 3;277(18):15482-5 PMID: 11854302
  26. Leukotriene BLT2 receptor monomers activate the G(i2) GTP-binding protein more efficiently than dimers.
    J Biol Chem. 2010 Feb 26;285(9):6337-47 PMID: 20026606
  27. The G protein-coupled receptor rhodopsin in the native membrane.
    FEBS Lett. 2004 Apr 30;564(3):281-288 PMID: 15111110
  28. Oligomerization of G-protein-coupled transmitter receptors.
    Nat Rev Neurosci. 2001 Apr;2(4):274-86 PMID: 11283750
  29. Three-dimensional membrane crystals in amphibian cone outer segments: 2. Crystal type associated with the saddle point regions of cone disks.
    Exp Eye Res. 1995 Sep;61(3):335-49 PMID: 7556497
  30. High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor.
    Science. 2007 Nov 23;318(5854):1258-65 PMID: 17962520
  31. The asymmetric/symmetric activation of GPCR dimers as a possible mechanistic rationale for multiple signalling pathways.
    Trends Pharmacol Sci. 2010 Jan;31(1):15-21 PMID: 19963287
  32. GPCR dimers fall apart.
    Sci Signal. 2010 Mar 30;3(115):pe12 PMID: 20354223
  33. G protein-coupled receptor hetero-dimerization: contribution to pharmacology and function.
    Br J Pharmacol. 2009 Sep;158(1):5-14 PMID: 19309353
  34. Oligomerization of G protein-coupled receptors: past, present, and future.
    Biochemistry. 2004 Dec 21;43(50):15643-56 PMID: 15595821
  35. Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor.
    Nature. 2000 Oct 26;407(6807):971-7 PMID: 11069170
  36. Requirement of rigid-body motion of transmembrane helices for light activation of rhodopsin.
    Science. 1996 Nov 1;274(5288):768-70 PMID: 8864113
  37. In vivo assembly of rhodopsin from expressed polypeptide fragments.
    Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3204-8 PMID: 7724540
  38. Characterisation of an improved two-dimensional p22121 crystal from bovine rhodopsin.
    J Mol Biol. 1998 Oct 9;282(5):991-1003 PMID: 9753549
  39. GABA(B) receptors function as a heteromeric assembly of the subunits GABA(B)R1 and GABA(B)R2.
    Nature. 1998 Dec 17;396(6712):674-9 PMID: 9872315
  40. Heterodimerization is required for the formation of a functional GABA(B) receptor.
    Nature. 1998 Dec 17;396(6712):679-82 PMID: 9872316
  41. Structural basis for parathyroid hormone-related protein binding to the parathyroid hormone receptor and design of conformation-selective peptides.
    J Biol Chem. 2009 Oct 9;284(41):28382-28391 PMID: 19674967
  42. Transducin activation by nanoscale lipid bilayers containing one and two rhodopsins.
    J Biol Chem. 2007 May 18;282(20):14875-81 PMID: 17395586
  43. Atomic-force microscopy: Rhodopsin dimers in native disc membranes.
    Nature. 2003 Jan 9;421(6919):127-8 PMID: 12520290
  44. G protein coupled receptor structure and activation.
    Biochim Biophys Acta. 2007 Apr;1768(4):794-807 PMID: 17188232
  45. The role of hormone receptors and GTP-regulatory proteins in membrane transduction.
    Nature. 1980 Mar 6;284(5751):17-22 PMID: 6101906
  46. Metabotropic glutamate receptor 5 is a disulfide-linked dimer.
    J Biol Chem. 1996 Nov 8;271(45):28612-6 PMID: 8910492
  47. Towards a view of functioning dimeric metabotropic receptors.
    Curr Opin Neurobiol. 2005 Jun;15(3):289-95 PMID: 15922585
  48. Instability of a class a G protein-coupled receptor oligomer interface.
    Mol Pharmacol. 2009 Jun;75(6):1296-9 PMID: 19273553
  49. A cell surface inactive mutant of the human lutropin receptor (hLHR) attenuates signaling of wild-type or constitutively active receptors via heterodimerization.
    Cell Signal. 2009 Nov;21(11):1663-71 PMID: 19616090
  50. Rescue of defective G protein-coupled receptor function in vivo by intermolecular cooperation.
    Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2319-24 PMID: 20080658
  51. A monomeric G protein-coupled receptor isolated in a high-density lipoprotein particle efficiently activates its G protein.
    Proc Natl Acad Sci U S A. 2007 May 1;104(18):7682-7 PMID: 17452637
Article Info
Journal
Trends in biochemical sciences
Abbr.
Trends Biochem Sci
ISSN
0968-0004
Published
2010-11-00
Epub
2010-00-09
Pages
595-600
Language
English
Region
England
NLM ID
7610674
PMCID
PMC2937196
Subset
IM
Grants
NEI NIH HHS · R01 EY008061 · United States
NIGMS NIH HHS · R01 GM079191 · United States
NIGMS NIH HHS · GM079191 · United States
NEI NIH HHS · R01-EY0008061 · United States
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