Interactions between selectivity filter and pore helix control filter gating in the MthK channel

Area of Science:

• Biophysics
• Molecular Biology
• Structural Biology

Background:

• C-type inactivation limits potassium (K+) channel activity by affecting the selectivity filter.
• The structural basis of selectivity filter gating in many K+ channels remains unclear.
• Previous studies linked KcsA channel inactivation to a collapsed selectivity filter.

Purpose of the Study:

• To investigate selectivity filter gating in the MthK potassium channel and its V55E mutant.
• To elucidate the structural mechanisms underlying K+ channel inactivation and conductance.
• To compare MthK gating mechanisms with those of the KcsA channel.

Main Methods:

• Electrophysiological recordings to measure channel activity.
• Molecular dynamics simulations to analyze atomistic behavior.
• Comparative analysis of wild-type (WT) MthK and MthK V55E mutant.

Main Results:

• MthK V55E exhibits lower open probability and unitary conductance than WT MthK.
• Two distinct side chain orientations of E55 in V55E alter K+ permeation and filter stability.
• Inactivation in both MthK WT and V55E is associated with a widened selectivity filter, contrasting with KcsA.

Conclusions:

• The E55 side chain orientation significantly impacts MthK channel conductance and inactivation.
• MthK inactivation involves selectivity filter widening, suggesting a conserved mechanism across K+ channels.
• Findings provide insights into the structural basis of K+ channel gating and inactivation.