Absence of calcium-sensing receptor basal activity due to inter-subunit disulfide bridges.

ABSTRACT: G protein-coupled receptors naturally oscillate between inactive and active states, often resulting in receptor constitutive activity with important physiological consequences. Among the class C G protein-coupled receptors that typically sense amino-acids and their derivatives, the calcium sensing receptor (CaSR) tightly controls blood calcium levels. Its constitutive activity has not yet been studied. Here, we demonstrate the importance of the inter-subunit disulfide bridges in maintaining the inactive state of CaSR, resulting in undetectable constitutive activity, unlike the other class C receptors. Deletion of these disulfide bridges results in strong constitutive activity that is abolished by mutations preventing amino acid binding. It shows that this inter-subunit disulfide link is ne

SUBMITTER: Ma S 

PROVIDER: S-EPMC11045811 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature