University of Dundee
School of Life Sciences
Computational Biology
Ion permeation across the membrane during electric and non-electric signaling
Thursday, January 10
2 PM
RRI 101
Abstract: Cells in higher organisms must be able to communicate both with each other and with the external world. A multitude of signaling pathways exist within eukaryotic cells, but the exchange of information across the cell membrane requires the function of specialized membrane proteins. The main routes for transmembrane signal transduction are via electric impulses, triggered by the function of ion channels, and by G-protein coupled receptor signaling. Due to their instrumental role, these membrane proteins represent the most important and abundant pharmaceutical targets in humans.
Our recent atomistic molecular simulations under transmembrane voltage and electrochemical gradients -- spanning several hundreds of microseconds and encompassing ~7,000 individual ion permeation events -- revealed key aspects of the fundamental mechanisms of both ion channel action and G-protein coupled receptor signal transduction. For instance, the exquisite selectivity and high conductance of potassium channels are indispensable features for the generation of sharp electric action potentials in electrically excitable cells such as neurons. I will first present a unified model of potassium channel permeation, in which these two -- seemingly contradictory -- characteristics emerge as the natural consequence of a single conduction mechanism. Small genomic differences in the regions coding for the channel selectivity filters lead to subtle deviations from this key mechanism, which underlie the observed spectrum from high to low-selectivity channels found in many organisms. Intriguingly, at the heart of both electric and GPCR-based signal transduction processes, new similarities begin to emerge that entail finely controlled ion transfer processes across the cell membrane.
Host: Seva Katritch
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