Co-evolution of ligand-receptor pairs

摘要: Specific receptors for lutropin (luteinizing hormone; LH) and follitropin (follicle-stimulating FSH) mediate the actions of human chorionic gonadotropin (hCG) FSH5 on gonads. Here we report that short independent sequences beta-subunit enable hCG to distinguish between FSH LH. Residues 11th 12th cysteines restrict receptor binding; residues 10th and, a much lesser extent, carboxy-terminal cysteine also affect LH binding. CF101-109, an analogue containing hFSH beta cysteines, had high affinity both receptors. Modifications CF101-109 reduce binding either or yield analogues having differing ratios LH:FSH activity. Ligand-binding specificity is determined by encoded parts exons 2-4 7-9 which prevent but have little effect controlled primarily 5 6 These determinants can be interchanged create bind hFSH. Our observations support model in distinct negative ligand-receptor interaction. This explains coevolution families homologous ligands their Natural designed manipulation these leads 'evolution' new, specific protein-protein interactions.