Lipid-protein forces predict conformational changes in a mechanosensitive channel

Eur Biophys J. 2021 Mar;50(2):181-186. doi: 10.1007/s00249-020-01488-z. Epub 2020 Dec 23.

Abstract

The mechanosensitive TREK-2 potassium channel, a member of the K2P family, has essential physiological roles and is, therefore, a pharmaceutical target. A combination of experimental and computational studies have established that of the two known conformations, "up" and "down", membrane tension directly favors the "up" state, which displays a higher conductance. However, these studies did not reveal the exact mechanism by which the membrane affects the channel conformation. In this work, we show that changes in protein-lipid interaction patterns suffice in predicting this conformational change, and pinpoint potentially important residues involved in this phenomenon.

Keywords: Conformational change; Force distribution analysis; Functional mode analysis; Ion channel; Membrane tension.

MeSH terms

  • Ion Channel Gating*
  • Lipid Metabolism*
  • Mechanotransduction, Cellular*
  • Membrane Proteins / metabolism*

Substances

  • Membrane Proteins