on conduction in a bacterial sodium channel在细菌钠通道传导.pdfVIP

On Conduction in a Bacterial Sodium Channel 1,2 1 Simone Furini , Carmen Domene * 1 Physical and Theoretical Chemistry Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom, 2 Department of Medical Surgery and Bioengineering, University of Siena, Siena, Italy 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. Selective permeability of Na+ over Ca2+ or K+ ions is essential for the biological + + function of Na -channels. After the emergence of the first high-resolution structure of a Na -channel, an anionic coordination site was proposed to confer Na+ selectivity through partial dehydration of Na+ via its direct interaction with conserved glutamate side chains. By combining molecular dynamics simulations and free-energy calculations, a low-energy permeation pathway for Na+ ion translocation through the selectivity filter of the recently determined crystal structure of a prokaryotic sodium channel from Arcobacter butzleri is characterised. The picture that emerges is that of a pore preferentially occupied by two ions, which can switch between different configurations by crossing low free-energy barriers. In contrast to K+ + -channels, the movements of the ions appear to be weakly coupled in Na -channels. When the free-energy maps for Na+ and K+ ions are compared, a selective