Heat-dependent opening of TRPV1 in the presence of capsaicin.

ABSTRACT: Transient receptor potential vanilloid member 1 (TRPV1) is a Ca²⁺-permeable cation channel that serves as the primary heat and capsaicin sensor in humans. Using cryo-EM, we have determined the structures of apo and capsaicin-bound full-length rat TRPV1 reconstituted into lipid nanodiscs over a range of temperatures. This has allowed us to visualize the noxious heat-induced opening of TRPV1 in the presence of capsaicin. Notably, noxious heat-dependent TRPV1 opening comprises stepwise conformational transitions. Global conformational changes across multiple subdomains of TRPV1 are followed by the rearrangement of the outer pore, leading to gate opening. Solvent-accessible surface area analyses and functional studies suggest that a subset of residues form an interaction network tha

SUBMITTER: Kwon DH 

PROVIDER: S-EPMC8335751 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature