Central cavity dehydration as a gating mechanism of potassium channels

• Published in: Nature communications Vol. 14; no. 1; pp. 2178 - 12
• Main Authors: Gu, Ruo-Xu, de Groot, Bert L.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.04.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 119/118; 631/57/2266; 631/57/2283; 639/638/563/981; Channel gating; Charged particles; Dehydration; Drying; Humanities and Social Sciences; Hydration; Hydrophobicity; Ion channels; Ion currents; Ions; Molecular dynamics; multidisciplinary; Occlusion; Permeation; Potassium; Potassium channels; Science; Science (multidisciplinary); Simulation; Structure-function relationships
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-37531-8

The hydrophobic gating model, in which ion permeation is inhibited by the hydrophobicity, rather than a physical occlusion of the nanopore, functions in various ion channels including potassium channels. Available research focused on the energy barriers for ion/water conduction due to the hydrophobicity, whereas how hydrophobic gating affects the function and structure of channels remains unclear. Here, we use potassium channels as examples and conduct molecular dynamics simulations to investigate this problem. Our simulations find channel activities (ion currents) highly correlated with cavity hydration level, implying insufficient hydration as a barrier for ion permeation. Enforced cavity dehydration successfully induces conformational transitions between known channel states, further implying cavity dewetting as a key step in the gating procedure of potassium channels utilizing different activation mechanisms. Our work reveals how the cavity dewetting is coupled to structural changes of potassium channels and how it affects channel activity. The conclusion may also apply to other ion channels. The hydrophobic gating is believed to function in various ion channels. Here, the authors use MD simulations to assess how dewetting of the channel pore modulates the function and conformational transition of the potassium channels.