Autoproteolysis and Intramolecular Dissociation of Yersinia YscU Precedes Secretion of Its C-Terminal Polypeptide YscUCC 英文参考文献.docVIP

Autoproteolysis and Intramolecular Dissociation of Yersinia YscU Precedes Secretion of Its C-Terminal Polypeptide YscUCC 英文参考文献.doc

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Autoproteolysis and Intramolecular Dissociation of Yersinia YscU Precedes Secretion of Its C-Terminal Polypeptide YscUCC 英文参考文献

AutoproteolysisandIntramolecularDissociationof YersiniaYscUPrecedesSecretionofItsC-Terminal PolypeptideYscUCC StefanFrost1,OanhHo2,Fre′de′ricH.Login1,ChristophF.Weise2,HansWolf-Watz1*,MagnusWolf- Watz2* 1DepartmentofMolecularBiologyandTheLaboratoryforMolecularInfectionMedicineSweden(MIMS),Umea?University,Umea?,Sweden,2DepartmentofChemistry, ChemicalBiologicalCenter,Umea? University,Umea?, Sweden Abstract Type III secretion system mediated secretion and translocation of Yop-effector proteins across the eukaryotic target cell membrane by pathogenic Yersinia is highly organized and is dependent on a switching event from secretion of early structural substrates to late effector substrates (Yops). Substrate switching can be mimicked invitro by modulating the calcium levelsin thegrowth medium. YscU that is essential for regulation of this switch undergoes autoproteolysis at a conserved NqPTH motif, resulting in a 10kDa C-terminal polypeptide fragment denoted YscUCC. Here we show that depletion of calcium induces intramolecular dissociation of YscUCC from YscU followed by secretion of the YscUCC polypeptide.Thus,YscUCCbehavedinvivoasaYopproteinwithrespecttosecretionproperties.Further,destabilizedyscU mutants displayed increased rates of dissociation of YscUCC invitro resulting in enhanced Yop secretion invivo at 30uC relative to the wild-type strain.These findings provide strong support to the relevance of YscUCC dissociation for Yop secretion.WeproposethatYscUCC orchestratesablockinthesecretionchannelthatiseliminatedbycalciumdepletion. Further,thestrikinghomologybetweendifferentmembersoftheYscU/FlhBfamilysuggeststhatthisproteinfamilypossess regulatoryfunctionsalsoinotherbacteriausingcomparablemechanisms. Citation:FrostS,HoO,LoginFH,WeiseCF,Wolf-WatzH,etal.(2012)AutoproteolysisandIntramolecularDissociationofYersiniaYscUPrecedesSecretionofItsC- TerminalPolypeptideYscUCC.PLoSONE7(11):e49349.doi:10.1371/journal.pone.0049349 Editor:EricCascales,CentreNationaldelaRecherche

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