Regensburg 2016 – wissenschaftliches Programm

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BP: Fachverband Biologische Physik

BP 27: Computational Biophysics

BP 27.1: Hauptvortrag

Dienstag, 8. März 2016, 09:30–10:00, H43

Membrane proteins under voltage: simulations of ion channels and receptors at work — •Ulrich Zachariae — University of Dundee, Edinburgh, United Kingdom

Electrochemical ion gradients across biological membranes generate membrane voltage and drive the function of essential membrane proteins. We use sustained transmembrane electrochemical gradients in molecular dynamics simulations to investigate the function of ion channels and receptors under voltage. In our work on potassium channels, we find that a mechanism involving electrostatic interaction between close ion pairs in the ion selectivity filter underlies high-efficiency conduction near the diffusion limit. Evidence for the existence of close ion contacts additionally comes from crystallography. We show that this mechanism is also exquisitely selective for the conduction of potassium vs. sodium ions. Our simulations reveal the determinants of ion discrimination in the channels under actual permeation conditions.

While voltage sensing in ion channels is a widely studied phenomenon, the effects of membrane voltage on other membrane proteins are not as well understood. G-protein coupled receptors (GPCRs), which transduce signals across the membrane and form most human drug targets, have been shown to be regulated by voltage as well. However, the nature of the voltage sensor has remained elusive. Our simulations reveal the motion of a conserved voltage-sensor in class A GPCRs, whose functional implications will be discussed.