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Papers of the Week

Papers: 10 Jul 2021 - 16 Jul 2021

Pharmacology/Drug Development

2021 Jul 08

Nat Struct Mol Biol

Editor's Pick

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


Kwon D H, Zhang F, Suo Y, Bouvette J, Borgnia MJ, Lee S-Y
Nat Struct Mol Biol. 2021 Jul 08.
PMID: 34239123.


Transient receptor potential vanilloid member 1 (TRPV1) is a Ca-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 that is directly involved in heat sensing. Our study provides a glimpse of the molecular principles underlying noxious physical and chemical stimuli sensing by TRPV1, which can be extended to other thermal sensing ion channels.