Seminar by Prof. Gerhard Thiel

Membrane Biophysics, TU Darmstadt, Germany

The physico-chemical nature of filter gating in K⁺ channels

The activity of K⁺ channels is determined by two gates, one at the exit from the cavity into the cytosol (inner gate) and one in the selectivity filter (filter gate). To understand the structure/function correlates of the filter gate we use a pore only K⁺ channel, which is made of only 82 amino acids per monomer and lacks an inner gate. The structural and functional simplicity of the protein with only one gate, provides in combination with high resolution single channel analysis, point mutations and computational methods an ideal system for understand filter gating. Our current data advocate a mechanism according to which filter gating is determined by a mutual interplay of ion permeation and binding to sites in the filter. An interesting feature of this model system is that the lifetime of an open state of the filter gate is in the sub µs time range, e.g. a time window which can be resolved in channel recordings and molecular dynamic (MD) simulations. This provides an interesting case for a direct comparison of experimental and computational data.