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-Structure paper
Title | Heat-dependent opening of TRPV1 in the presence of capsaicin. |
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Journal, issue, pages | Nat Struct Mol Biol, Vol. 28, Issue 7, Page 554-563, Year 2021 |
Publish date | Jul 8, 2021 |
Authors | Do Hoon Kwon / Feng Zhang / Yang Suo / Jonathan Bouvette / Mario J Borgnia / Seok-Yong Lee / |
PubMed Abstract | 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 ...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. |
External links | Nat Struct Mol Biol / PubMed:34239123 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.63 - 3.72 Å |
Structure data | EMDB-23473, PDB-7lp9: EMDB-23474, PDB-7lpa: EMDB-23475, PDB-7lpb: EMDB-23476, PDB-7lpc: EMDB-23477: EMDB-23478, PDB-7lpd: EMDB-23479, PDB-7lpe: |
Chemicals | ChemComp-T7X: ChemComp-LBN: ChemComp-6OU: ChemComp-NA: ChemComp-YFP: ChemComp-4DY: |
Source |
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Keywords | MEMBRANE PROTEIN / Heat sensing ion channel |