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Structure paper

TitleMolecular details of ruthenium red pore block in TRPV channels.
Journal, issue, pagesEMBO Rep, Vol. 25, Issue 2, Page 506-523, Year 2024
Publish dateJan 15, 2024
AuthorsRuth A Pumroy / José J De Jesús-Pérez / Anna D Protopopova / Julia A Rocereta / Edwin C Fluck / Tabea Fricke / Bo-Hyun Lee / Tibor Rohacs / Andreas Leffler / Vera Moiseenkova-Bell /
PubMed AbstractTransient receptor potential vanilloid (TRPV) channels play a critical role in calcium homeostasis, pain sensation, immunological response, and cancer progression. TRPV channels are blocked by ...Transient receptor potential vanilloid (TRPV) channels play a critical role in calcium homeostasis, pain sensation, immunological response, and cancer progression. TRPV channels are blocked by ruthenium red (RR), a universal pore blocker for a wide array of cation channels. Here we use cryo-electron microscopy to reveal the molecular details of RR block in TRPV2 and TRPV5, members of the two TRPV subfamilies. In TRPV2 activated by 2-aminoethoxydiphenyl borate, RR is tightly coordinated in the open selectivity filter, blocking ion flow and preventing channel inactivation. In TRPV5 activated by phosphatidylinositol 4,5-bisphosphate, RR blocks the selectivity filter and closes the lower gate through an interaction with polar residues in the pore vestibule. Together, our results provide a detailed understanding of TRPV subfamily pore block, the dynamic nature of the selectivity filter and allosteric communication between the selectivity filter and lower gate.
External linksEMBO Rep / PubMed:38225355 / PubMed Central
MethodsEM (single particle)
Resolution2.65 - 3.47 Å
Structure data

29046

8ffl

EMDB-29046, PDB-8ffl:
Wildtype rat TRPV2 in nanodiscs bound to RR
Method: EM (single particle) / Resolution: 3.47 Å

29047

8ffm

EMDB-29047, PDB-8ffm:
Wildtype rat TRPV2 in nanodiscs bound to RR and 2-APB
Method: EM (single particle) / Resolution: 2.9 Å

29048

8ffn

EMDB-29048, PDB-8ffn:
RR-bound wildtype rabbit TRPV5 in nanodiscs
Method: EM (single particle) / Resolution: 2.96 Å

29051

8ffq

EMDB-29051, PDB-8ffq:
Wildtype rabbit TRPV5 into nanodiscs in the presence of PI(4,5)P2 and ruthenium red
Method: EM (single particle) / Resolution: 2.65 Å

Chemicals

ChemComp-PEX:
1,2-DIDECANOYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE

ChemComp-FZ4:
2-aminoethyl diphenylborinate

ChemComp-R2R:
ruthenium(6+) azanide pentaamino(oxido)ruthenium (1/4/2)

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

ChemComp-ERG:
ERGOSTEROL

ChemComp-CPL:
1-PALMITOYL-2-LINOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE / phospholipid*YM

Source
  • rattus norvegicus (Norway rat)
  • oryctolagus cuniculus (rabbit)
KeywordsMEMBRANE PROTEIN / TRPV2 / TRPV5 / TRP Channel / Ruthenium Red / 2-APB / PI(4 / 5)P2

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