Probing the Mechanism of Gating in Sodium Channels by Experiment and Computation

Abstract

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. 





References:
[1]

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.

[2]

 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.

[3]

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

[4]

S. Furini, C. Domene (2012) On conduction and selectivity in sodium channels. PLoS Comput Biol, 2012.

[5]

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


Biological Areas:

Physiology
Structural Biology

BBSRC Area:

Molecules, cells and industrial biotechnology