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Schlagwörter:
cholecystokinin; CCK; CCK-15; G-protein coupled receptor; NMR solution structure
Zusammenfassung:
Conformational features of the C-terminal carboxyamidated pentadecapeptide of CCK ((SHRISDRD)-H-19[SO4]-YMGWMDF(33)-NH2) were determined by NMR spectroscopy in a zwitterionic membrane- mimetic solvent system, composed of DPC micelles. The C- terminal octapeptide consisted of a well-defined pseudohelix that was nearly identical to the structure previously reported for nonsulfated CCK-8 in the same solvent system. N-terminal amino acids of CCK-15 were highly disordered, with no clear conformational preference. Extensive NOE-restrained molecular dynamics simulations of the CCK-15/CCK1-R complex suggested that almost all the experimentally determined intermolecular contact points provided by NMR, site-directed mutagenesis, and photo-affinity labeling could be simultaneously satisfied, when the N-terminus of the ligand is placed in close spatial proximity to the N-terminus of the receptor. (C) 2002 Elsevier Science (USA). All rights reserved.
