Conformation of a peptide ligand bound to its G-protein coupled receptor
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(1-21)NH2, bound to a PACAP-specific receptor by NMR spectroscopy. Residues 3-7 form a unique...
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Veröffentlicht in: | Nature Structural Biology 2001-02, Vol.8 (2), p.161-165 |
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Sprache: | eng |
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Zusammenfassung: | 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(1-21)NH2, bound to a PACAP-specific receptor by NMR spectroscopy. Residues 3-7 form a unique β-coil structure that is preceded by an N-terminal extended tail. This β-coil creates a patch of hydrophobic residues that is important for receptor binding. In contrast, the C-terminal region (residues 8-21) forms an α-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. |
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ISSN: | 1072-8368 1545-9993 2331-365X 1545-9985 |
DOI: | 10.1038/84159 |