Structural highlights
Function
VIP_HUMAN VIP causes vasodilation, lowers arterial blood pressure, stimulates myocardial contractility, increases glycogenolysis and relaxes the smooth muscle of trachea, stomach and gall bladder.[1] PHM and PHV also cause vasodilation. PHM-27 is a potent agonist of the calcitonin receptor CALCR, with similar efficacy as calcitonin.[2]
Publication Abstract from PubMed
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 alpha-helix, micelle-bound VIP-G has a curved alpha-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.
Structural difference of vasoactive intestinal peptide in two distinct membrane-mimicking environments.,Umetsu Y, Tenno T, Goda N, Shirakawa M, Ikegami T, Hiroaki H Biochim Biophys Acta. 2011 May;1814(5):724-30. Epub 2011 Mar 23. PMID:21439408[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ma JN, Currier EA, Essex A, Feddock M, Spalding TA, Nash NR, Brann MR, Burstein ES. Discovery of novel peptide/receptor interactions: identification of PHM-27 as a potent agonist of the human calcitonin receptor. Biochem Pharmacol. 2004 Apr 1;67(7):1279-84. PMID:15013843 doi:http://dx.doi.org/10.1016/j.bcp.2003.11.008
- ↑ Ma JN, Currier EA, Essex A, Feddock M, Spalding TA, Nash NR, Brann MR, Burstein ES. Discovery of novel peptide/receptor interactions: identification of PHM-27 as a potent agonist of the human calcitonin receptor. Biochem Pharmacol. 2004 Apr 1;67(7):1279-84. PMID:15013843 doi:http://dx.doi.org/10.1016/j.bcp.2003.11.008
- ↑ Umetsu Y, Tenno T, Goda N, Shirakawa M, Ikegami T, Hiroaki H. Structural difference of vasoactive intestinal peptide in two distinct membrane-mimicking environments. Biochim Biophys Acta. 2011 May;1814(5):724-30. Epub 2011 Mar 23. PMID:21439408 doi:10.1016/j.bbapap.2011.03.009
