Conformational switches in the VPAC1 receptor

Authors


Ingrid Langer, IRIBHM, ULB, 808 route de Lennik CP 602, B-1070 Brussels, Belgium. E-mail: ilanger@ulb.ac.be

Abstract

The vasoactive intestinal peptide receptor 1 (VPAC1) belongs to family B of GPCRs and is activated upon binding of vasoactive intestinal peptide (VIP) and pituitary AC-activating polypeptide neuropeptides. Widely distributed throughout body, VPAC1 plays important regulatory roles in human physiology and physiopathology. Like most members of the GPCR-B family, VPAC1 receptor is predicted to follow the actual paradigm of a common ‘two-domain’ model of natural ligand action. However the precise structural basis for ligand binding, receptor activation and signal transduction are still incompletely understood due in part to the absence of X-ray crystal structure of the whole receptor and to significant structural differences with the most extensively studied family of receptor, the GPCR-A/rhodopsin family. Here, we try to summarize the current knowledge of the molecular mechanisms involved in VPAC1 receptor activation and signal transduction. This includes search for amino acids involved in the two-step process of VIP binding, in the stabilization of VPAC1 inactive and active conformations, and in binding and activation of G proteins.

LINKED ARTICLES This article is part of a themed section on Secretin Family (Class B) G Protein-Coupled Receptors. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.166.issue-1

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