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-Structure paper
タイトル | Molecular details of ruthenium red pore block in TRPV channels. |
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ジャーナル・号・ページ | EMBO Rep, Vol. 25, Issue 2, Page 506-523, Year 2024 |
掲載日 | 2024年1月15日 |
著者 | Ruth 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 要旨 | 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 ...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. |
リンク | EMBO Rep / PubMed:38225355 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.65 - 3.47 Å |
構造データ | EMDB-29046, PDB-8ffl: EMDB-29047, PDB-8ffm: EMDB-29048, PDB-8ffn: EMDB-29051, PDB-8ffq: |
化合物 | ChemComp-PEX: ChemComp-FZ4: ChemComp-R2R: ChemComp-POV: ChemComp-ERG: ChemComp-CPL: |
由来 |
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キーワード | MEMBRANE PROTEIN / TRPV2 / TRPV5 / TRP Channel / Ruthenium Red / 2-APB / PI(4 / 5)P2 |