@article{TEXTUAL, recid = {13322}, author = {Lau, Carus H. Y. and Flood, Emelie and Hunter, Mark J. and Williams-Noonan, Billy J. and Corbett, Karen M. and Ng, Chai-Ann and Bouwer, James C. and Stewart, Alastair G. and Perozo, Eduardo and Allen, Toby W. and Vandenberg, Jamie I.}, title = {Potassium dependent structural changes in the selectivity filter of HERG potassium channels}, journal = {Nature Communications}, address = {2024-08-29}, number = {TEXTUAL}, abstract = {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<sup>+</sup> 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.}, url = {http://knowledge.uchicago.edu/record/13322}, }