GSK1702934A and M085 directly activate TRPC6 via a mechanism of stimulating the extracellular cavity formed by the pore helix and transmembrane helix S6.

ABSTRACT: Transient receptor potential canonical (TRPC) channels, as important membrane proteins regulating intracellular calcium (Ca²⁺_i) signaling, are involved in a variety of physiological and pathological processes. Activation and regulation of TRPC are more dependent on membrane or intracellular signals. However, how extracellular signals regulate TRPC6 function remains to be further investigated. Here, we suggest that two distinct small molecules, M085 and GSK1702934A, directly activate TRPC6, both through a mechanism of stimulation of extracellular sites formed by the pore helix (PH) and transmembrane (TM) helix S6. In silico docking scanning of TRPC6 identified three extracellular sites that can bind small molecules, of which only mutations on residues of PH and S6 heli

SUBMITTER: Yang PL 

PROVIDER: S-EPMC8458982 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature