One-two punch of techniques helps pin down the activated configuration of KcsA ion channel
One-two punch of techniques helps pin down the activated configuration of KcsA ion channel lead image
Extensive study of the KcsA potassium channel has advanced general understanding of ion channels. However, the exact configuration of the channel’s activated state remains elusive due to its short lifetime.
Pérez-Conesa et al. wanted to identify the dominant activated configuration of the KcsA ion channel in solid state NMR (ssNMR) spectrometry experiments, which allow the study of membrane proteins in their native environment.
They obtained ssNMR spectra of the ion channel under activating conditions but did not attempt to interpret the structure of the activated channel from the spectra using standard methods. Instead, they ran molecular dynamics simulations of potential activated state structures and predicted chemical shifts. They compared the chemical shifts estimated with simulation to the chemical shifts from the ssNMR experiments with Bayesian statistics.
The authors found the chemical shifts of the simulated partially open state structures are more compatible with the ssNMR chemical shifts than the chemical shifts of the fully open state structures. This suggests the activated state in ssNMR is closer to the partially open state than the fully open state.
“The other important aspect of this work is that we introduce an analysis pipeline that could be useful when chemical shifts obtained under different conditions are available and several different candidate structures cannot be distinguished a priori,” said author Lucie Delemotte. “It’s also a nice demonstration of the combination of two techniques that are powerful on their own, but even more so when combined.”
The authors plan to use this combination to study how lipids control the channel’s protein configuration.
Source: “Informing NMR experiments with molecular dynamics simulations to characterize the dominant activated state of the KcsA ion channel,” by Sergio Pérez-Conesa, Eric G. Keeler, Dongyu Zhang, Lucie Delemotte, and Ann E. McDermott, Journal of Chemical Physics (2021). The article can be accessed at https://aip.scitation.org/doi/full/10.1063/5.0040649 .
This paper is part of the Special Collection in Honor of Women in Chemical Physics and Physical Chemistry, learn more here .
