Work

Conformational Transitions of the Pituitary Adenylate Cyclase-Activating Polypeptide Receptor, a Human Class B GPCR

Year: 2017

Type: article

Abstract: The G protein-coupled pituitary adenylate cyclase-activating polypeptide receptor (PAC1R) is a potential therapeutic target for endocrine, metabolic and stress-related disorders. However, many questions regarding the protein structure and dynamics of PAC1R remain largely unanswered. Using microsecond-long simulations, we examined the open and closed PAC1R conformations interconnected within an ensemble of transitional states. The open-to-closed transition can be initiated by "unzipping" the extracellular domain and the transmembrane domain, mediated by a unique segment within the β3-β4 loop. Transitions between different conformational states range between microseconds to milliseconds, which clearly implicate allosteric effects propagating from the extracellular face of the receptor to the intracellular G protein-binding site. Such allosteric dynamics provides structural and mechanistic insights for the activation and modulation of PAC1R and related class B receptors.

Source: Scientific Reports

DOI: 10.1038/s41598-017-05815-x

Authors: Chenyi Liao, Xiaochuan Zhao, Matthias Brewer, Victor May, Jianing Li

Institution: University of Vermont

Language: English

Topic: Receptor Mechanisms and Signaling

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $2,690