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TitleExtracellular cap domain is an essential component of the TRPV1 gating mechanism.
Journal, issue, pagesNat Commun, Vol. 12, Issue 1, Page 2154, Year 2021
Publish dateApr 12, 2021
AuthorsKirill D Nadezhdin / Arthur Neuberger / Yury A Nikolaev / Lyle A Murphy / Elena O Gracheva / Sviatoslav N Bagriantsev / Alexander I Sobolevsky /
PubMed AbstractTransient receptor potential (TRP) channels are polymodal molecular sensors involved in numerous physiological processes and implicated in a variety of human diseases. Several structures of the ...Transient receptor potential (TRP) channels are polymodal molecular sensors involved in numerous physiological processes and implicated in a variety of human diseases. Several structures of the founding member of the TRP channel family, TRPV1, are available, all of which were determined for the protein missing the N- and C-termini and the extracellular S5-P-loop. Here, we present structures of the full-length thirteen-lined ground squirrel TRPV1 solved by cryo-EM. Our structures resolve the extracellular cap domain formed by the S5-P-loops and the C-terminus that wraps around the three-stranded β-sheet connecting elements of the TRPV1 intracellular skirt. The cap domain forms a dome above the pore's extracellular entrance, with four portals leading to the ion conductance pathway. Deletion of the cap increases the TRPV1 average conductance, reduces the open probability and affects ion selectivity. Our data show that both the termini and the cap domain are critical determinants of TRPV1 function.
External linksNat Commun / PubMed:33846324 / PubMed Central
MethodsEM (single particle)
Resolution3.19 - 3.81 Å
Structure data

EMDB-23491, PDB-7lqy:
Structure of squirrel TRPV1 in apo state
Method: EM (single particle) / Resolution: 3.19 Å

EMDB-23492, PDB-7lqz:
Structure of squirrel TRPV1 in complex with RTX
Method: EM (single particle) / Resolution: 3.41 Å

EMDB-23493, PDB-7lr0:
Structure of squirrel TRPV1 in complex with capsaicin
Method: EM (single particle) / Resolution: 3.81 Å

Chemicals

ChemComp-POV:
(2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / phospholipid*YM / POPC

ChemComp-YBG:
1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoinositol

ChemComp-CL:
Unknown entry / Chloride

ChemComp-NA:
Unknown entry

ChemComp-6EU:
resiniferatoxin / toxin*YM / Resiniferatoxin

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

Source
  • ictidomys tridecemlineatus (thirteen-lined ground squirrel)
  • Homo sapiens (human)
KeywordsMEMBRANE PROTEIN / Transient Receptor Potential V Family Member 1 / TRP channel / TRPV1 full length / TRPV1 wild type / RTX / resiniferatoxin / capsaicin

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