On Conduction in a Bacterial Sodium Channel 英文参考文献.docVIP

OnConductioninaBacterialSodiumChannel SimoneFurini1,2,CarmenDomene1* 1Physical and Theoretical Chemistry Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom, 2Department of Medical Surgery and Bioengineering,UniversityofSiena,Siena,Italy Abstract Voltage-gatedNa+-channelsaretransmembraneproteinsthatareresponsibleforthefastdepolarizingphaseoftheaction potential in nerve and muscular cells. Selective permeability of Na over Ca 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 + 2+ + + + + + coordinationsitewasproposedtoconferNa selectivitythroughpartialdehydrationofNa viaitsdirectinteractionwith conservedglutamatesidechains.Bycombiningmoleculardynamicssimulationsandfree-energycalculations,alow-energy permeationpathwayforNa iontranslocationthroughtheselectivityfilteroftherecentlydeterminedcrystalstructureofa + prokaryotic sodium channel from Arcobacter butzleri is characterised. The picture that emerges is that of a pore preferentiallyoccupiedbytwoions,whichcanswitchbetweendifferentconfigurationsbycrossinglowfree-energybarriers. + + IncontrasttoK -channels,themovementsoftheionsappeartobeweaklycoupledinNa -channels.Whenthefree-energy maps for Na and K ions are compared, a selective site is characterised in the narrowest region of the filter, where a hydratedNa ion,andnotahydratedK ion,isenergeticallystable. + + + + Citation:FuriniS,DomeneC(2012)OnConductioninaBacterialSodiumChannel.PLoSComputBiol8(4):e1002476.doi:10.1371/journal.pcbi.1002476 Editor:DennisRLivesay,UNCCharlotte,UnitedStatesofAmerica ReceivedDecember27,2011;AcceptedFebruary26,2012;PublishedApril5,2012 Copyright: ? 2012 Furini, Domene. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. F