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1、Plasmidxxx(2013)xxx–xxxContentslistsavailableatSciVerseScienceDirectPlasmidjournalhomepage:www.elsevier.com/locate/yplasCleavageoftheantitoxinoftheparDtoxin–antitoxinsystemisdeterminedbytheClpAPproteaseandismodulatedbytherelativeratioofthetoxinandtheantitoxina,1,⇑abElizabethDiago-Navarro,
2、AnaMaríaHernández-Arriaga,SlawomirKubik,baIgorKonieczny,RamónDíaz-OrejasaDepartmentofMolecularMicrobiologyandInfectionBiology,CentrodeInvestigacionesBiológicas(CSIC),Madrid,SpainbDepartmentofMolecularandCellularBiology,IntercollegiateFacultyofBiotechnology,UniversityofGdansk,Gdansk,Poland
3、articleinfoabstractArticlehistory:DifferentialstabilityoftoxinsandantitoxinsisthekeyfortheconditionalactivationandAvailableonlinexxxxfunctionofToxin–Antitoxinsystems.HerewereporttheevaluationoftheactionofcellCommunicatedbyManuelEspinosaproteasesLon,ClpAP,ClpXPandClpYQontheKisantitoxinandt
4、heKidtoxinoftheparDTAsystemofplasmidR1.InvitroanalysisshowsthatKisantitoxin,butnottheKidtoxin,Keywords:iscleavedspecificallybytheClpAPprotease.TheKidtoxinisnotcleavedeitherbythispro-Toxin–antitoxinsystemsteaseorbyanyoftheotherscellproteasestestedbutincomplexwiththeKisantitoxinHostproteases
5、protectsthecleavageofthisproteininawaythatisdependentonthetoxin–antitoxinAntitoxinstabilityratio.WefurthershowthatthisprotectioniscorrelatedwiththeinabilityoftheClpAchap-PostsegregationalkillingPlasmidstabilityeronetoaccesstheKisantitoxinwhenincomplexwithKidtoxin.Thestabilityoftheanti-tox
6、ingreatlyincreasesinvivoinaclpP-backgroundandplasmidmaintenancemediatedbytheparDsystem,whichisdependentonthedifferentialdecayoftheantitoxin,isreducedtothelevelsobservedintheabsenceofafunctionaltoxin.Thefunctionalimplicationsofthesedataarefurtherdiscussedwithintheframeoftheregulationofthep
7、arDsystemandoftheavailableinformationonthenatureofthetoxin–antitoxincomplexesformedatdifferenttoxin–antitoxinratios.Ó2013ElsevierInc.Allrightsreserved.1.Introductionaregenerallybicistronicoperonsencodingtwoproteins:anantitoxinandatoxin.ToxintargetscouldvaryfromoneTo