The human VPAC1 receptor: identification of the N-terminal ectodomain as a major VIP-binding site by photoaffinity labeling and 3D modeling.
The human VPAC1 receptor for VIP and PACAP is a class II Gprotein-coupled receptor (GPCR). The N-terminal ectodomain of the VPAC1 receptor plays a crucial role in VIP binding. Photoaffinity experiments clearly indicated that the 6-28 part of VIP physically interacts with the N-terminal ectodomain. Construction of a 3D model of the N-terminal ectodomain of VPAC1 receptor based on the NMR structure of the mouse CRF receptor 2 indicated the presence of short consensus repeat/Sushi domain. Docking of VIP in the N-terminal ectodomain structural model was performed taking into account the severe constraints provided by photoaffinity. A VIP-binding site was identified on the side of the structured core of the N-terminal ectodomain of the receptor.
Couvineau
Alain
A
INSERM U773, Faculté de Médecine X. Bichat, 16 rue Henri Huchard, 75018 Paris, France. Alain.Couvineau@bichat.inserm.fr
Tan
Yossan-Var
YV
Ceraudo
Emille
E
Lacapère
Jean-Jacques
JJ
Murail
Samuel
S
Neumann
Jean-Michel
JM
Laburthe
Marc
M
D000818:Animals; D001665:Binding Sites; D006801:Humans; D021621:Imaging, Three-Dimensional; D051379:Mice; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D019920:Photoaffinity Labels; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000737:chemistry* / Q000378:metabolism*
D019920:Photoaffinity Labels; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D014660:Vasoactive Intestinal Peptide