GPC receptors and not ligands decide the binding mode in neuropeptide Y multireceptor/multiligand system.

摘要: Many G protein-coupled receptors belong to families of different receptor subtypes, which are recognized by a variety distinct ligands. To study such multireceptor/multiligand system, we investigated the Y-receptor family. This family consists four Y in humans (hY 1R, hY 2R, 4R, and 5R) is activated so-called NPY hormone family, itself three native peptide ligands named neuropeptide (NPY), pancreatic polypeptide (PP), YY (PYY). The 5R shows high affinity for all ligands, although PP binding, slightly decreased. As rational explanation, suggest that Tyr (27) lost as contact point between contrast or PYY. Furthermore, several important residues ligand binding were identified first extensive mutagenesis 5R. Using complementary approach, able discover novel interaction NPY. NPY(Arg (25)) 5R(Asp (2.68)) well (33)) (6.59)) maintained PYY but PP-hY 4R NPY-hY 1R points. Therefore, provide evidence subtype not pre-orientated conformation at membrane decides mode. model was set up on basis crystal structure bovine rhodopsin. We can show most be critical located within now postulated pocket.