Molecular details of ruthenium red pore block in TRPV channels.
EMBO Rep
; 25(2): 506-523, 2024 Feb.
Article
em En
| MEDLINE
| ID: mdl-38225355
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Canais de Potencial de Receptor Transitório
/
Antineoplásicos
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article