Molecular Basis of Class B GPCR Selectivity for the Neuropeptides PACAP and VIP.

ABSTRACT: The related neuropeptides PACAP and VIP, and their shared PAC1, VPAC1 and VPAC2 receptors, regulate a large array of physiological activities in the central and peripheral nervous systems. However, the lack of comparative and molecular mechanistic investigations hinder further understanding of their preferred binding selectivity and function. PACAP and VIP have comparable affinity at the VPAC1 and VPAC2 receptor, but PACAP is 400-1,000 fold more potent than VIP at the PAC1 receptor. A molecular understanding of the differing neuropeptide-receptor interactions and the details underlying the receptor transitions leading to receptor activation are much needed for the rational design of selective ligands. To these ends, we have combined structural information and advanced simulation techniques

SUBMITTER: Liao C 

PROVIDER: S-EPMC8027070 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature