TY - JOUR
T1 - Molecular details of ruthenium red pore block in TRPV channels
AU - Pumroy, Ruth A.
AU - De Jesús-Pérez, José J.
AU - Protopopova, Anna D.
AU - Rocereta, Julia A.
AU - Fluck, Edwin C.
AU - Fricke, Tabea
AU - Lee, Bo Hyun
AU - Rohacs, Tibor
AU - Leffler, Andreas
AU - Moiseenkova-Bell, Vera
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/2/13
Y1 - 2024/2/13
N2 - 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.
AB - 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.
KW - Channel Activation and Blocking
KW - Cryo-Electron Microscopy
KW - Pore Blocker
KW - Ruthenium Red
KW - TRPV Channels
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U2 - 10.1038/s44319-023-00050-0
DO - 10.1038/s44319-023-00050-0
M3 - Article
C2 - 38225355
AN - SCOPUS:85185196294
SN - 1469-221X
VL - 25
SP - 506
EP - 523
JO - EMBO Reports
JF - EMBO Reports
IS - 2
ER -