Paper Citing NAMD - Abstract
Ceraudo, Emilie; Murail, Samuel; Tan, Yossan-Var; Lacapere, Jean-Jacques; Neumann, Jean-Michel; Couvineau, Alain; Laburthe, Marc
The vasoactive intestinal peptide (VIP) alpha-helix up to C terminus interacts with the N-terminal ectodomain of the human VIP/Pituitary adenylate cyclase-activating peptide 1 receptor: Photoaffinity, molecular modeling, and dynamics
MOLECULAR ENDOCRINOLOGY, 22:147-155, JAN 2008
The neuropeptide vasoactive intestinal peptide (VIP) strongly impacts on human pathophysiology and does so through interaction with class II G protein-coupled receptors. We characterized the C terminus-binding site of VIP in the N-terminal ectodomain (N-ted) of the human VPAC1 receptor: 1) The probe [I-125-Bpa(28)] VIP in which the C-terminal residue (Asn(28)) is substituted by a photoreactive p-benzoyl-L-Phe(Bpa) was used to photolabel the receptor. After receptor cleavage and Edman sequencing, it was shown that Asn(28) of VIP is in contact with Lys(127) in the receptor N-ted. Taking into account previous data, it follows that the C-terminal and central parts of VIP from Asn(28) to Phe(6) lie in the N-ted. 2) A three-dimensional model of the N-ted was constructed, the fold being identified as a Sushi domain with two antiparallel beta-sheets and three disulfide bonds. The nuclear magnetic resonance structure of VIP was then docked into this model by taking into account the constraint provided by photoaffinity experiments with [I-125-Bpa(28)] VIP. It appeared that VIP runs parallel to the beta 3-beta 4 antiparallel sheets. 3) We performed molecular dynamic simulations over 14 nsec of the complex between VIP and receptor N-ted and the free N-ted. The structural model of the free N-ted is stable, and VIP tends to further stabilize the N-ted structure more especially in the loops connecting the beta-sheets. These structural studies provide a detailed molecular understanding of the VIP-receptor interaction.
