Flexibility of the N-Terminal mVDAC1 Segment Controls the Channel’s Gating Behavior 英文参考文献.docVIP

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Flexibility of the N-Terminal mVDAC1 Segment Controls the Channel’s Gating Behavior 英文参考文献.doc

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Flexibility of the N-Terminal mVDAC1 Segment Controls the Channel’s Gating Behavior 英文参考文献

FlexibilityoftheN-TerminalmVDAC1SegmentControls theChannel’sGatingBehavior BarbaraMertins.,GeorgiosPsakis.,WolfgangGrosse,KatrinChristianeBack,AnastasiaSalisowski, PhilippReiss,UlrichKoert,Lars-OliverEssen* DepartmentofChemistry,PhilippsUniversityMarburg,Marburg,Germany Abstract Sincethesolutionofthemolecularstructuresofmembersofthevoltagedependentanionchannels(VDACs),theN-terminal a-helixhasbeenthemainfocusofattention,sinceitsstrategiclocation,incombinationwithitsputativeconformational flexibility,coulddefineorcontrolthechannel’sgatingcharacteristics.Throughengineeringoftwodouble-cysteinemVDAC1 variantsweachievedfixingoftheN-terminalsegmentatthebottomandmidpointofthepore.Whilstcross-linkingatthe midpointresultedinthechannelremainingconstitutivelyopen,cross-linkingatthebaseresultedinan‘‘asymmetric’’gating behavior, with closure only at one electric fields orientation depending on the channel’s orientation in the lipid bilayer. Additionally,andwhilethenativechanneladoptsseveralwell-definedclosedstates(S1andS2),thecross-linkedvariants showeduponclosureaclearpreferencefortheS2state.Withnative-channelcharacteristicsrestoredfollowingreductionof thecysteines,itisevidentthattheconformationalflexibilityoftheN-terminalsegmentplaysindeedamajorpartinthe controlofthechannel’sgatingbehavior. Citation: Mertins B, Psakis G, Grosse W, Back KC, Salisowski A, et al. (2012) Flexibility of the N-Terminal mVDAC1 Segment Controls the Channel’s Gating Behavior.PLoSONE7(10):e47938.doi:10.1371/journal.pone.0047938 Editor:ZheZhang,VirginiaCommonwealthUniversity,UnitedStatesofAmerica ReceivedJuly16,2012;AcceptedSeptember25,2012;PublishedOctober23,2012 Copyright: ? 2012 Mertins et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding: This work was funded by the Deutsche Forschungsgemeinschaft (ES 152/8-1 and KO 134