冠状病毒Coronavirusl论文-2013 Ion Channels Formed by SARS Coronavirus Envelope Protein_ Lipid Regulation of Conductance and Selectivity.pdf

冠状病毒Coronavirusl论文-2013 Ion Channels Formed by SARS Coronavirus Envelope Protein_ Lipid Regulation of Conductance and Selectivity.pdf

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时间:2020-03-16

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1、632aWednesday,February6,2013Cx26(hCx26)channelsseemstorepresentthechannelwithopengates.Thisincreasedgjby1.6-foldwithEC50of2.3M,whileitsmodifiedform1,2-cyclo-structure,andmoleculardynamicsstudiesbasedonit,revealthatchargedres-hexanedione(BSA-CHD),whichdoesnotbindAA,wasineff

2、ective.Voltageidues(D46,E47,R75,R184)attheextracellularentranceoftheaqueouspore-sensitivegatingofCx36GJswasreducedbySCCAandBSAthatexplaininaregionthoughttobeinvolvedingatingrearrangements-formanelectrostaticparttheirgj-enhancingeffect.TheinhibitionofCx36GJchannelsbyAAnetw

3、ork.WeexploredtheroleofthesesaltbridgeinteractionsingatingusingcanberescuedbyBSAbutnotbyBSA-CHD.MAFPandthapsigargin,inhib-mutagenesis,kineticanalysisandchemicalmodifications.Substitutionofneu-itorandactivatorofAAsynthesisviaphospholipaseA2,increasedandreducedtralresiduesfo

4、rD46orE47,whichwouldeliminatetheirparticipationinsaltgj,respectively.WeassumethatendogenousAAisoneofkeyfactorsleadingbridges,acceleratedeactivationkineticsandmoderatelyincreasetheapparenttolowfunctionalefficacyofCx36GJchannelsundercontrolconditions.2þaffinityofCatoinducecha

5、nnelclosing.ThesedatasupportaroleoftheseFurthermore,wesuggestthatgj-enhancingeffectofBSAandMAFPmayberesiduesinstabilizationoftheopenstate.Inaddition,whenD46issubstitutedrelatedwithreductionofAAlevels,whileSCCAslimitAA’saccessibilitytobyacysteine(D46C),modificationbyMTSESto

6、addanegativechargein-itsbindingsiteonCx36.creasesholdingandtailcurrents.Thissuggeststhatanegativechargeatthispositionisinvolvedinstabilizingopenhemichannels.Inwild-typechannels,3249-PosBoardB404followingdepolarizingpulsesto0mV,peaktailcurrentsincreaseasafunctionIonChannel

7、sFormedbySARSCoronavirusEnvelopeProtein:Lipidofpulseduration,reachingmaximumwithpulsesof40sec.Strikingly,E47A/QRegulationofConductanceandSelectivitymutationsshowedpeaktailcurrentsthatsaturatemorerapidly,at15sec,sug-CarminaVerdia´-Ba´guena1,JoseL.Nieto-Torres2,AntonioAlcar

8、az1,gestingthatthispositionalsoplaysakeyroleinhemichannelactivation.ThusMartaL.DeDiego2,LuisEnju

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