人类VPAC1受体：通过光亲和标记和三维建模确定N端胞外域为主要的血管活性肠肽结合位点

The human VPAC1 receptor: identification of the N-terminal ectodomain as a major VIP-binding site by photoaffinity labeling and 3D modeling.

作者信息

Couvineau Alain, Tan Yossan-Var, Ceraudo Emille, Lacapère Jean-Jacques, Murail Samuel, Neumann Jean-Michel, Laburthe Marc

机构信息

INSERM U773, Faculté de Médecine X. Bichat, 16 rue Henri Huchard, 75018 Paris, France.

出版信息

Ann N Y Acad Sci. 2006 Jul;1070:205-9. doi: 10.1196/annals.1317.015.

DOI:10.1196/annals.1317.015

PMID:16888167

Abstract

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.

摘要

人源的血管活性肠肽（VIP）和垂体腺苷酸环化酶激活肽（PACAP）的VPAC1受体是一种II类G蛋白偶联受体（GPCR）。VPAC1受体的N端胞外结构域在VIP结合中起关键作用。光亲和实验清楚地表明，VIP的6 - 28部分与N端胞外结构域发生物理相互作用。基于小鼠促肾上腺皮质激素释放因子（CRF）受体2的核磁共振（NMR）结构构建的VPAC1受体N端胞外结构域的三维模型表明存在短共有重复序列/寿司结构域。考虑到光亲和提供的严格限制条件，在N端胞外结构域结构模型中对VIP进行对接。在受体N端胞外结构域的结构化核心一侧鉴定出一个VIP结合位点。