title: Structural difference of vasoactive intestinal peptide in two distinct membrane-mimicking environments.
abstract: Vasoactive intestinal peptide (VIP) is a 28-amino acid neuropeptide which belongs to a glucagon/secretin superfamily, the ligand of class II G protein-coupled receptors. Knowledge for the conformation of VIP bound to membrane is important because the receptor activation is initiated by membrane binding of VIP. We have previously observed that VIP-G (glycine-extended VIP) is unstructured in solution, as evidenced by the limited NMR chemical shift dispersion. In this study, we determined the three-dimensional structures of VIP-G in two distinct membrane-mimicking environments. Although these are basically similar structures composed of a disordered N-terminal region and a long α-helix, micelle-bound VIP-G has a curved α-helix. The side chains of residues Phe(6), Tyr(10), Leu(13), and Met(17) found at the concave face form a hydrophobic patch in the micelle-bound state. The structural differences in two distinct membrane-mimicking environments show that the micelle-bound VIP-G localized at the water-micelle boundary with these side chains toward micelle interior. In micelle-bound PACAP-38 (one of the glucagon/secretin superfamily peptide) structure, the identical hydrophobic residues form the micelle-binding interface. This result suggests that these residues play an important role for the membrane binding of VIP and PACAP.
authors: Graduate School of Medicine, Kobe University, Chuo-ku, Kobe, Hyogo, Japan.
authors: Yoshitaka
authors: Y
authors: Umetsu
authors: Takeshi
authors: T
authors: Tenno
authors: Natsuko
authors: N
authors: Goda
authors: Masahiro
authors: M
authors: Shirakawa
authors: Takahisa
authors: T
authors: Ikegami
authors: Hidekazu
authors: H
authors: Hiroaki
mesh_terms: D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D018005:Receptors, Vasoactive Intestinal Peptide / Q000737:chemistry / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008823:Micelles; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide