Instability of a Class A G Protein-Coupled Receptor Oligomer Interface
- 9 March 2009
- journal article
- Published by American Society for Pharmacology & Experimental Therapeutics (ASPET)
- Vol. 75 (6), 1296-1299
- https://doi.org/10.1124/mol.108.053876
Abstract
The quaternary structure of G protein-coupled receptors (GPCRs) can influence their trafficking and ability to transduce signals. GPCR oligomers are generally portrayed as long-lived entities, although the stability of these complexes has not been studied. Here we show that D2 dopamine receptor protomers interact transiently at a specific oligomer interface. Selective immobilization of cyan fluorescent protein-D2 receptors (C-D2Rs) in the plasma membrane failed to completely immobilize coexpressed D2-venus receptors (D2R-Vs), suggesting that the two did not form stable oligomers with each other. Oxidative cross-linking stabilized C-D2R-D2R-V oligomers such that immobilization of C-D2R also immobilized D2R-V. This stabilization required the presence in both C-D2R and D2R-V of a cysteine residue in transmembrane domain 4 (TM4), a region identified as a putative oligomer interface in these and other class A GPCRs. These results suggest that the interaction of D2 receptor protomers at TM4 is transient unless stabilized and that the quaternary structure of these receptors may thus be subject to physiological or pharmacological regulation.Keywords
This publication has 13 references indexed in Scilit:
- Analysis of receptor oligomerization by FRAP microscopyNature Methods, 2009
- How and why do GPCRs dimerize?Trends in Pharmacological Sciences, 2008
- Identification of a serotonin/glutamate receptor complex implicated in psychosisNature, 2008
- Reprint of “Crystal packing analysis of Rhodopsin crystals” [J. Struct. Biol. 158 (2007) 455–462]Journal of Structural Biology, 2007
- G protein-coupled receptor dimerisation: Molecular basis and relevance to functionBiochimica et Biophysica Acta (BBA) - Biomembranes, 2006
- Opsin is present as dimers in COS1 cells: Identification of amino acids at the dimeric interfaceProceedings of the National Academy of Sciences, 2006
- Crosstalk in G protein-coupled receptors: Changes at the transmembrane homodimer interface determine activationProceedings of the National Academy of Sciences, 2005
- Diversifying the repertoire of G protein-coupled receptors through oligomerizationProceedings of the National Academy of Sciences, 2005
- Organization of the G Protein-coupled Receptors Rhodopsin and Opsin in Native MembranesJournal of Biological Chemistry, 2003
- Oligomerization of G-protein-coupled transmitter receptorsNature Reviews Neuroscience, 2001