Mechanism of sensitivity modulation in the calcium-sensing receptor via electrostatic tuning.

ABSTRACT: Transfer of information across membranes is fundamental to the function of all organisms and is primarily initiated by transmembrane receptors. For many receptors, how ligand sensitivity is fine-tuned and how disease associated mutations modulate receptor conformation to allosterically affect receptor sensitivity are unknown. Here we map the activation of the calcium-sensing receptor (CaSR) - a dimeric class C G protein-coupled receptor (GPCR) and responsible for maintaining extracellular calcium in vertebrates. We show that CaSR undergoes unique conformational rearrangements compared to other class C GPCRs owing to specific structural features. Moreover, by analyzing disease associated mutations, we uncover a large permissiveness in the architecture of the extracellular domain of CaSR, wi

SUBMITTER: Schamber MR 

PROVIDER: S-EPMC9033857 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature