Year: 2013
Type: article
Abstract: Voltage-gated potassium channels form potassium-selective pores in cell membranes. They open or close in response to changes in the transmembrane potential and are essential for generating action potentials, and thus for the functioning of heart and brain. While a mechanism for how these channels close has been proposed, it is not clear what drives their opening. Here we use free energy molecular dynamics simulations to show that work must be done on the pore to reduce the kink in the pore-lining (S6) α-helices, thereby forming the helix bundle crossing and closing the channel. Strain is built up as the pore closes, which subsequently drives opening. We also determine the effect of mutating the PVPV motif that causes the kink in the S6 helix. Finally, an approximate upper limit on how far the S4 helix is displaced as the pore closes is estimated. Voltage-gated potassium channels open and close in response to changes in transmembrane potential, but their opening mechanism is poorly understood. Here, free energy molecular dynamics simulations show that strain accumulates as the pore closes, which subsequently drives opening.
Source: Nature Communications
DOI: 10.1038/ncomms2858
Authors: Philip W. Fowler, Mark S. P. Sansom
Institution: University of Oxford
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $6,990
Awards: Ion channels: structure to function via biomolecular simulations., G111866060, G1778333383, Ion channels: structure to function via biomolecular simulations., Simulations for Synthetic Biology: Mapping Biological Switches, OMSys: Towards a systems model of a bacterial outer membrane, G7080100828, G712558274, G8080688728, MemProtMD: A resource for membrane proteins, G8858561294
OpenAlex ID: W2010718509