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-Structure paper
タイトル | Electromechanical coupling in the hyperpolarization-activated K channel KAT1. |
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ジャーナル・号・ページ | Nature, Vol. 583, Issue 7814, Page 145-149, Year 2020 |
掲載日 | 2020年5月27日 |
著者 | Michael David Clark / Gustavo F Contreras / Rong Shen / Eduardo Perozo / |
PubMed 要旨 | Voltage-gated potassium (K) channels coordinate electrical signalling and control cell volume by gating in response to membrane depolarization or hyperpolarization. However, although voltage-sensing ...Voltage-gated potassium (K) channels coordinate electrical signalling and control cell volume by gating in response to membrane depolarization or hyperpolarization. However, although voltage-sensing domains transduce transmembrane electric field changes by a common mechanism involving the outward or inward translocation of gating charges, the general determinants of channel gating polarity remain poorly understood. Here we suggest a molecular mechanism for electromechanical coupling and gating polarity in non-domain-swapped K channels on the basis of the cryo-electron microscopy structure of KAT1, the hyperpolarization-activated K channel from Arabidopsis thaliana. KAT1 displays a depolarized voltage sensor, which interacts with a closed pore domain directly via two interfaces and indirectly via an intercalated phospholipid. Functional evaluation of KAT1 structure-guided mutants at the sensor-pore interfaces suggests a mechanism in which direct interaction between the sensor and the C-linker hairpin in the adjacent pore subunit is the primary determinant of gating polarity. We suggest that an inward motion of the S4 sensor helix of approximately 5-7 Å can underlie a direct-coupling mechanism, driving a conformational reorientation of the C-linker and ultimately opening the activation gate formed by the S6 intracellular bundle. This direct-coupling mechanism contrasts with allosteric mechanisms proposed for hyperpolarization-activated cyclic nucleotide-gated channels, and may represent an unexpected link between depolarization- and hyperpolarization-activated channels. |
リンク | Nature / PubMed:32461693 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.5 - 3.8 Å |
構造データ | EMDB-21018, PDB-6v1x: EMDB-21019, PDB-6v1y: |
化合物 | ChemComp-QNP: ChemComp-QNJ: |
由来 |
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キーワード | TRANSPORT PROTEIN / membrane protein / voltage-gated ion channel / potassium channel |