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-Structure paper
タイトル | Potassium dependent structural changes in the selectivity filter of HERG potassium channels. |
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ジャーナル・号・ページ | Nat Commun, Vol. 15, Issue 1, Page 7470, Year 2024 |
掲載日 | 2024年8月29日 |
著者 | Carus H Y Lau / Emelie Flood / Mark J Hunter / Billy J Williams-Noonan / Karen M Corbett / Chai-Ann Ng / James C Bouwer / Alastair G Stewart / Eduardo Perozo / Toby W Allen / Jamie I Vandenberg / |
PubMed 要旨 | The fine tuning of biological electrical signaling is mediated by variations in the rates of opening and closing of gates that control ion flux through different ion channels. Human ether-a-go-go ...The fine tuning of biological electrical signaling is mediated by variations in the rates of opening and closing of gates that control ion flux through different ion channels. Human ether-a-go-go related gene (HERG) potassium channels have uniquely rapid inactivation kinetics which are critical to the role they play in regulating cardiac electrical activity. Here, we exploit the K sensitivity of HERG inactivation to determine structures of both a conductive and non-conductive selectivity filter structure of HERG. The conductive state has a canonical cylindrical shaped selectivity filter. The non-conductive state is characterized by flipping of the selectivity filter valine backbone carbonyls to point away from the central axis. The side chain of S620 on the pore helix plays a central role in this process, by coordinating distinct sets of interactions in the conductive, non-conductive, and transition states. Our model represents a distinct mechanism by which ion channels fine tune their activity and could explain the uniquely rapid inactivation kinetics of HERG. |
リンク | Nat Commun / PubMed:39209832 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.0 - 3.5 Å |
構造データ | EMDB-45597: Cryo-EM structure of the human ether-a-go-go related K+ channel (hERG) in 300 mM K+ EMDB-45598: Cryo-EM structure of the human ether-a-go-go related K+ channel (hERG) in 3 mM K+ EMDB-45599: Cryo-EM structure of the human ether-a-go-go related K+ channel (hERG) in 300 mM K+ without symmetry EMDB-45600: Cryo-EM structure of the human ether-a-go-go related K+ channel (hERG) in 3 mM K+ without symmetry |
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