Dual Chaperone Role of the C-Terminal Propeptide in Folding and Oligomerization of the Pore-Forming Toxin Aerolysin 英文参考文献.docVIP

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Dual Chaperone Role of the C-Terminal Propeptide in Folding and Oligomerization of the Pore-Forming Toxin Aerolysin 英文参考文献.doc

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Dual Chaperone Role of the C-Terminal Propeptide in Folding and Oligomerization of the Pore-Forming Toxin Aerolysin 英文参考文献

DualChaperoneRoleoftheC-TerminalPropeptidein FoldingandOligomerizationofthePore-FormingToxin Aerolysin IoanIacovache1.,MatteoT.Degiacomi2.,LucilePernot1¤,SylviaHo1,MarcSchiltz3,MatteoDalPeraro2*, F.GisouvanderGoot1* 1Global Health Institute, EcolePolytechniqueFe′de′raledeLausanne,Lausanne,Switzerland, 2Institute ofBioengineering, Ecole Polytechnique Fe′de′rale deLausanne, Lausanne,Switzerland,3LaboratoiredeCristallographie,EcolePolytechniqueFe′de′raledeLausanne,Lausanne,Switzerland Abstract Throughoutevolution,oneofthemostancientformsofaggressionbetweencellsororganismshasbeentheproduction ofproteinsorpeptidesaffectingthepermeabilityofthetargetcellmembrane.Thisclassofvirulencefactorsincludesthe largestfamilyofbacterialtoxins,thepore-formingtoxins(PFTs).PFTsarebistablestructuresthatcanexistinasolubleand a transmembrane state. It is unclear what drives biosynthetic folding towards the soluble state, a requirement that is essential toprotectthePFT-producing cell.Herewehaveinvestigated thefoldingofaerolysin,producedbythehuman pathogen Aeromonas hydrophila, and more specifically the role of the C-terminal propeptide (CTP). By combining the predictive power of computational techniques with experimental validation using both structural and functional approaches,weshowthattheCTPpreventsaggregationduringbiosyntheticfolding.Weidentifiedspecificresiduesthat mediatebindingoftheCTPtothetoxin.WeshowthattheCTPiscrucialforthecontroloftheaerolysinactivity,sinceit protects individual subunitsfromaggregation withinthebacteriumandlatercontrolsassemblyofthequaternary pore- formingcomplexatthesurfaceofthetargethostcell.TheCTPisthefirstexampleofaC-terminalchain-linkedchaperone with dualfunction. Citation:IacovacheI,DegiacomiMT,PernotL,HoS,SchiltzM,etal.(2011)DualChaperoneRoleoftheC-TerminalPropeptideinFoldingandOligomerizationof thePore-FormingToxinAerolysin.PLoSPathog7(7):e1002135.doi:10.1371/journal.ppat.1002135 Editor:CraigR.Roy,YaleUniversitySchoolofMedicine,UnitedStatesof