Molecular details of ruthenium red pore block in TRPV channelsopen access
- Authors
- Pumroy, Ruth A; De Jesús-Pérez, José J; Protopopova, Anna D; Rocereta, Julia A; Fluck, Edwin C; Fricke, Tabea; Lee, Bo-Hyun; Rohacs, Tibor; Leffler, Andreas; Moiseenkova-Bell, Vera
- Issue Date
- Feb-2024
- Publisher
- Springer Nature
- Keywords
- Channel Activation and Blocking; Cryo-Electron Microscopy; Pore Blocker; Ruthenium Red; TRPV Channels
- Citation
- EMBO Reports, v.25, no.2, pp 506 - 523
- Pages
- 18
- Indexed
- SCIE
SCOPUS
- Journal Title
- EMBO Reports
- Volume
- 25
- Number
- 2
- Start Page
- 506
- End Page
- 523
- URI
- https://scholarworks.gnu.ac.kr/handle/sw.gnu/69813
- DOI
- 10.1038/s44319-023-00050-0
- ISSN
- 1469-221X
1469-3178
- 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. © The Author(s) 2024.
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