Towards understanding the role of the first extracellular loop for the binding of peptide hormones to G-protein coupled receptors.
By a combination of molecular modelling and site-directed mutagenesis studies, we have recently identified a key residue in the first extracellular loop which determines agonist selectivity and high-affinity binding in the V1a vasopressin receptor. Based on primary sequence analysis and structure-activity relationship studies of other neuropeptides and their receptors, the corresponding amino acid in the first extracellular loop is proposed to play a homologous role in conferring affinity and selectivity. This would seem to be the case notably for angiotensin, cholecystokinin, neuropeptide Y and neurokinin receptors.
D000595:Amino Acid Sequence; D000818:Animals; D005110:Extracellular Space / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D013552:Swine; D014982:Xenopus laevis
D006728:Hormones; D010455:Peptides; D011956:Receptors, Cell Surface; D019204:GTP-Binding Proteins