Allosteric sodium binding cavity in GPR3: a novel player in modulation of Aβ production.

ABSTRACT: The orphan G-protein coupled receptor 3 (GPR3) belongs to class A G-protein coupled receptors (GPCRs) and is highly expressed in central nervous system neurons. Among other functions, it is likely associated with neuron differentiation and maturation. Recently, GPR3 has also been linked to the production of Aβ peptides in neurons. Unfortunately, the lack of experimental structural information for this receptor hampers a deep characterization of its function. Here, using an in-silico and in-vitro combined approach, we describe, for the first time, structural characteristics of GPR3 receptor underlying its function: the agonist binding site and the allosteric sodium binding cavity. We identified and validated by alanine-scanning mutagenesis the role of three functionally relevant residues: C

SUBMITTER: Capaldi S 

PROVIDER: S-EPMC6056553 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature