Cross-Reactivity of Anthrax and C2 Toxin Protective Antigen Promotes the Uptake of Botulinum C2I Toxin into Human Endothelial Cells 英文参考文献.docVIP

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Cross-Reactivity of Anthrax and C2 Toxin Protective Antigen Promotes the Uptake of Botulinum C2I Toxin into Human Endothelial Cells 英文参考文献.doc

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Cross-Reactivity of Anthrax and C2 Toxin Protective Antigen Promotes the Uptake of Botulinum C2I Toxin into Human Endothelial Cells 英文参考文献

Cross-ReactivityofAnthraxandC2Toxin:Protective AntigenPromotestheUptakeofBotulinumC2IToxin intoHumanEndothelialCells AngelikaKronhardt1.,MonicaRolando2,3.,ChristophBeitzinger1,CarolineStefani2,MichaelLeuber1, GillesFlatau2,MichelR.Popoff4,RolandBenz1,5*,EmmanuelLemichez2,3,6 * 1Rudolf-Virchow-Center,UniversityofWu¨rzburg,Wu¨rzburg,Germany,2Inserm,U895,ToxinesMicrobiennesdanslaRelationHo?te-Pathoge`nes,BatimentArchimed,Nice, France,3Faculte′ deMe′decine, InstitutFe′de′ratifdeRecherche50,Universite′ deNice-SophiaAntipolis,Nice,France,4Unite′ desBacte′ries AnaerobiesetToxines,Institut Pasteur, Paris, France, 5School of Engineering and Science, Jacobs University Bremen, Bremen, Germany, 6Laboratoire central de bacte′riologie, Centre Hospitalier UniversitairedeNice,Nice,France Abstract Binary toxins are among the most potent bacterial protein toxins performing a cooperative mode of translocation and exhibitfatalenzymaticactivitiesineukaryoticcells.AnthraxandC2toxinarethemostprominentexamplesfortheAB7/8 typeoftoxins.TheBsubunitsbindbothhostcellreceptorsandtheenzymaticApolypeptidestotriggertheirinternalization andtranslocationintothehostcellcytosol.C2toxiniscomposedofanactinADP-ribosyltransferase(C2I)andC2IIbinding subunits.Anthraxtoxiniscomposedofadenylatecyclase(EF)andMAPKKprotease(LF)enzymaticcomponentsassociated toprotectiveantigen(PA)bindingsubunit.Thebindingandtranslocationcomponentsanthraxprotectiveantigen(PA63) andC2IIofC2toxinshareasequencehomologyofabout35%,suggestingthattheymightsubstituteforeachother.Here weshowbyconductinginvitromeasurementsthatPA63bindsC2IandthatC2IIcanbindbothEFandLF.Anthraxedema factor(EF)andlethalfactor(LF)havehigheraffinitiestobindtochannelsformedbyC2IIthanC2toxin’sC2Ibindstoanthrax protectiveantigen(PA63).Furthermore,wecoulddemonstratethatPAinhighconcentrationhastheabilitytotransportthe enzymatic moiety C2I into target cells, causing actin modification and cell rounding. In contrast, C2II does not show significantcapacitytopromote