Voltage-gated Na+-channels are transmembrane proteins that are responsible for the fast depolarizing phase of the action potential in nerve and muscular cells. In humans, mutations in these channels cause a wide rang of cardiovascular and neurological diseases. This project will entail both experimental techniques (molecular biology, biochemistry, crystallography) and computational methods (Molecular dynamics simulations and bioinformatics) to investigate the structure/function relationships, especially the permeation and gating processes, for voltage-gated sodium channels.
McCusker EC, Bagnéris C, Naylor CE, Cole AR, D'Avanzo N, Nichols CG, Wallace BA. Structure of a bacterial voltage-gated sodium channel pore reveals mechanisms of opening and closing. Nature Commun. 3, 1102.
Ulmschneider, M.B., Bagnéris, C., McCusker, E.C., DeCaen, P.G., Delling, M., Clapham, D.E., Ulmschneider, J.P. and Wallace, B.A. (2013) Molecular dynamics of ion transport through the open conformation of a bacterial voltage-gated sodium channel. Proc. Nat. Acad. Sci. USA 110, 6364-6369.
Bagnéris, C., DeCaen, P.G., Naylor, C.E., Pryde, D., Nobeli, I., Clapham, D.E., & Wallace, B.A. (2014) The prokaryotic NavMs channel as a structural and functional model for eukaryotic sodium channel antagonism. Proc. Natl. Acad. Sci. USA 111:8428-8433
S. Furini, C. Domene (2012) On conduction and selectivity in sodium channels. PLoS Comput Biol, 2012.
S. Furini, C. Domene (2011) Gating at the selectivity filter of ion channels that conduct Na+ and K+ ions. Biophys. J. 2011, 101, 1623-1631