Many peptide hormones elicit a wide array of physiological effects by binding to G-protein coupled receptors. We have determined the conformation of pituitary adenylate cyclase activating polypeptide, PACAP(I-ZI)NH2, bound to a PACAP-specific receptor by NMR spectroscopy. Residues 3-7 form a unique beta -coil structure that is preceded by an N-terminal extended tail. This beta -coil creates a patch of hydrophobic residues that is important for receptor binding. In contrast, the C-terminal region (residues 8-21) forms an ct-helix, similar to that in the micelle-bound PACAP. Thus, the conformational difference between PACAP in the receptor-bound and the micelle-bound states is limited to the N-terminal seven residues. This observation is consistent with the two-step ligand transportation model in which PACAP first binds to the membrane nonspecifically and then diffuses two-dimensionally in search of its receptor; a conformational change at the N-terminal region then allows specific interactions between the ligand and the receptor.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据