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Title | Extracellular cap domain is an essential component of the TRPV1 gating mechanism. |
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Journal, issue, pages | Nat Commun, Vol. 12, Issue 1, Page 2154, Year 2021 |
Publish date | Apr 12, 2021 |
Authors | Kirill D Nadezhdin / Arthur Neuberger / Yury A Nikolaev / Lyle A Murphy / Elena O Gracheva / Sviatoslav N Bagriantsev / Alexander I Sobolevsky / |
PubMed Abstract | 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 ...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 links | Nat Commun / PubMed:33846324 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.19 - 3.81 Å |
Structure data | EMDB-23491, PDB-7lqy: EMDB-23492, PDB-7lqz: EMDB-23493, PDB-7lr0: |
Chemicals | ChemComp-POV: ChemComp-YBG: ChemComp-CL: ChemComp-NA: ChemComp-6EU: ChemComp-4DY: |
Source |
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Keywords | MEMBRANE PROTEIN / Transient Receptor Potential V Family Member 1 / TRP channel / TRPV1 full length / TRPV1 wild type / RTX / resiniferatoxin / capsaicin |