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-Structure paper
| タイトル | Structural basis of voltage-dependent gating in BK channels. |
|---|---|
| ジャーナル・号・ページ | Nat Commun, Vol. 16, Issue 1, Page 5846, Year 2025 |
| 掲載日 | 2025年7月1日 |
著者 | Gustavo F Contreras / Rong Shen / Ramon Latorre / Eduardo Perozo / ![]() |
| PubMed 要旨 | The allosteric communication between the pore domain, voltage sensors, and Ca binding sites in the calcium- and voltage-activated K channel (BK) underlies its physiological role as the preeminent ...The allosteric communication between the pore domain, voltage sensors, and Ca binding sites in the calcium- and voltage-activated K channel (BK) underlies its physiological role as the preeminent signal integrator in excitable systems. BK displays shallow voltage sensitivity with very fast gating charge kinetics, yet little is known about the molecular underpinnings of this distinctive behavior. Here, we explore the mechanistic basis of coupling between voltage-sensing domains (VSDs) and calcium sensors in Aplysia BK by locking the VSDs in their activated (R196Q and R199Q) and resting (R202Q) states, with or without calcium. Cryo-EM structures of these mutants reveal unique tilts at the S4 C-terminal end, together with large side-chain rotameric excursions of the gating charges. Notably, the VSD resting structure (R202Q) also revealed BK in its elusive, fully closed state, highlighting the reciprocal relation between calcium and voltage sensors. These structures provide a plausible path where voltage and Ca binding couple energetically and define the conformation of the pore domain and, thus, BK's full functional range. |
リンク | Nat Commun / PubMed:40593533 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.6 - 3.5 Å |
| 構造データ | EMDB-46901, PDB-9di8: EMDB-46903, PDB-9dic: EMDB-46918, PDB-9dit: EMDB-46939, PDB-9djv: EMDB-46956, PDB-9dkf: EMDB-46961, PDB-9dkl: EMDB-46963, PDB-9dkn: |
| 化合物 | ![]() ChemComp-K: ![]() ChemComp-MG: ![]() ChemComp-CA: |
| 由来 |
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キーワード | MEMBRANE PROTEIN / Potassium Channel / Voltage sensor / calcium bound / open channel / calcium-activated / large conductance / transport protein |
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