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- Title
Conformation of a peptide ligand bound to its G-protein coupled receptor.
- Authors
Inooka, Hiroshi; Ohtaki, Tetsuya; Kitahara, Osamu; Ikegami, Takahisa; Endo, Satoshi; Kitada, Chieko; Ogi, Kazuhiro; Onda, Haruo; Fujino, Masahiko; Shirakawa, Masahiro
- Abstract
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.
- Subjects
PEPTIDE hormones; ADENYLATE cyclase; NUCLEAR magnetic resonance spectroscopy
- Publication
Nature Structural Biology, 2001, Vol 8, Issue 2, p161
- ISSN
1072-8368
- Publication type
Article
- DOI
10.1038/84159