Ligand sensitivity in dimeric associations of the serotonin 5HT2c receptor.
G-protein-coupled receptors (GPCRs) respond to external stimuli by activating heterotrimeric G proteins inside the cell. There is increasing evidence that many GPCRs exist as dimers or higher oligomers, but the biochemical nature of such dimers and what roles they have, if any, in signal transduction remains unclear. We conducted a comprehensive study of dimerization of the 5HT2c serotonin receptor using disulphide-trapping experiments. We found a dimer interface between transmembrane (TM) helices IV and V that is markedly sensitive to the state of receptor activation. This dimer seems to be quasisymmetrical in interfacial geometry and asymmetrical in its association with its cognate G alpha protein. We also found a second interface at TM I helices, which is insensitive to the state of activation.
Mancia
Filippo
F
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
Assur
Zahra
Z
Herman
Ariel G
AG
Siegel
Risa
R
Hendrickson
Wayne A
WA
D002460:Cell Line; D003545:Cysteine / Q000235:genetics; D019281:Dimerization; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008024:Ligands; D008958:Models, Molecular; D016296:Mutagenesis; D017434:Protein Structure, Tertiary; D044405:Receptor, Serotonin, 5-HT2C / Q000737:chemistry* / Q000378:metabolism*
D008024:Ligands; D044405:Receptor, Serotonin, 5-HT2C; D003545:Cysteine