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Structure paper

TitleHeat-dependent opening of TRPV1 in the presence of capsaicin.
Journal, issue, pagesNat Struct Mol Biol, Vol. 28, Issue 7, Page 554-563, Year 2021
Publish dateJul 8, 2021
AuthorsDo Hoon Kwon / Feng Zhang / Yang Suo / Jonathan Bouvette / Mario J Borgnia / Seok-Yong Lee /
PubMed AbstractTransient 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 linksNat Struct Mol Biol / PubMed:34239123 / PubMed Central
MethodsEM (single particle)
Resolution2.63 - 3.72 Å
Structure data

EMDB-23473, PDB-7lp9:
Cryo-EM structure of full-length TRPV1 at 4 degrees Celsius
Method: EM (single particle) / Resolution: 2.63 Å

EMDB-23474, PDB-7lpa:
Cryo-EM structure of full-length TRPV1 with capsaicin at 4 degrees Celsius
Method: EM (single particle) / Resolution: 3.37 Å

EMDB-23475, PDB-7lpb:
Cryo-EM structure of full-length TRPV1 with capsaicin at 25 degrees Celsius
Method: EM (single particle) / Resolution: 3.54 Å

EMDB-23476, PDB-7lpc:
Cryo-EM structure of full-length TRPV1 at 48 degrees Celsius
Method: EM (single particle) / Resolution: 3.06 Å

EMDB-23477:
Cryo-EM map of full-length TRPV1 with capsaicin at 48 degrees Celsius (10s), in an intermediate state
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-23478, PDB-7lpd:
Cryo-EM structure of full-length TRPV1 with capsaicin at 48 degrees Celsius, in an intermediate state, class 2
Method: EM (single particle) / Resolution: 3.55 Å

EMDB-23479, PDB-7lpe:
Cryo-EM structure of full-length TRPV1 with capsaicin at 48 degrees Celsius, in an open state, class 1
Method: EM (single particle) / Resolution: 3.72 Å

Chemicals

ChemComp-T7X:
Phosphatidylinositol

ChemComp-LBN:
1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine / phospholipid*YM

ChemComp-6OU:
[(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyloxy-propan-2-yl] (~{Z})-octadec-9-enoate / phospholipid*YM

ChemComp-NA:
Unknown entry

ChemComp-YFP:
1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol

ChemComp-4DY:
(6E)-N-(4-hydroxy-3-methoxybenzyl)-8-methylnon-6-enamide / neurotoxin*YM

Source
  • rattus norvegicus (Norway rat)
KeywordsMEMBRANE PROTEIN / Heat sensing ion channel

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