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Updated: Oct 31, 2025

Mutagenesis and Functional Analysis of Ion Channels Heterologously Expressed in Mammalian Cells
Published on: October 1, 2010
Unexpected Gating Behaviour of an Engineered Potassium Channel Kir
Charline Fagnen1,2, Ludovic Bannwarth1, Dania Zuniga1
1UMR 7590, CNRS, Muséum National d'Histoire Naturelle, Institut de Minéralogie, Physique des Matériaux et Cosmochimie, IMPMC, Sorbonne Université, Paris, France.
Abstract:
In this study, we investigated the dynamics and functional characteristics of the KirBac3.1 S129R, a mutated bacterial potassium channel for which the inner pore-lining helix (TM2) was engineered so that the bundle crossing is trapped in an open conformation. The structure of this channel has been previously determined at high atomic resolution. We explored the dynamical characteristics of this open state channel using an in silico method MDeNM that combines molecular dynamics simulations and normal modes. We captured the global and local motions at the mutation level and compared these data with HDX-MS experiments. MDeNM provided also an estimation of the probability of the different opening states that are in agreement with our electrophysiological experiments. In the S129R mutant, the Arg129 mutation releases the two constriction points in the channel that existed in the wild type but interestingly creates another restriction point.
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