Promiscuous G-protein activation by the calcium-sensing receptor.

ABSTRACT: The human calcium-sensing receptor (CaSR) detects fluctuations in the extracellular Ca²⁺ concentration and maintains Ca²⁺ homeostasis^1,2. It also mediates diverse cellular processes not associated with Ca²⁺ balance^3-5. The functional pleiotropy of CaSR arises in part from its ability to signal through several G-protein subtypes⁶. We determined structures of CaSR in complex with G proteins from three different subfamilies: G_q, G_i and G_s. We found that the homodimeric CaSR of each complex couples to a single G protein through a common mode. This involves the C-terminal helix of each Gα subunit binding to a shallow pocket that is formed in one CaSR subunit by all three intracellular loops (ICL1-

SUBMITTER: Zuo H 

PROVIDER: S-EPMC11844898 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature