Structural mechanism of cooperative activation of the human calcium-sensing receptor by Ca²⁺ ions and L-tryptophan.

ABSTRACT: The human calcium-sensing receptor (CaSR) is a class C G protein-coupled receptor (GPCR) responsible for maintaining Ca²⁺ homeostasis in the blood. The general consensus is that extracellular Ca²⁺ is the principal agonist of CaSR. Aliphatic and aromatic L-amino acids, such as L-Phe and L-Trp, increase the sensitivity of CaSR towards Ca²⁺ and are considered allosteric activators. Crystal structures of the extracellular domain (ECD) of CaSR dimer have demonstrated Ca²⁺ and L-Trp binding sites and conformational changes of the ECD upon Ca²⁺/L-Trp binding. However, it remains to be understood at the structural level how Ca²⁺/L-Trp binding to the ECD leads to conformational changes in transmembrane domains (TMDs) and consequent C

SUBMITTER: Ling S 

PROVIDER: S-EPMC8115157 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature