Illuminating the allosteric modulation of the calcium-sensing receptor.

ABSTRACT: Many membrane receptors are regulated by nutrients. However, how these nutrients control a single receptor remains unknown, even in the case of the well-studied calcium-sensing receptor CaSR, which is regulated by multiple factors, including ions and amino acids. Here, we developed an innovative cell-free Förster resonance energy transfer (FRET)-based conformational CaSR biosensor to clarify the main conformational changes associated with activation. By allowing a perfect control of ambient nutrients, this assay revealed that Ca²⁺ alone fully stabilizes the active conformation, while amino acids behave as pure positive allosteric modulators. Based on the identification of Ca²⁺ activation sites, we propose a molecular basis for how these different ligands cooperate to

SUBMITTER: Liu H 

PROVIDER: S-EPMC7474691 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature