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dc.contributor.authorListon, Sean D.
dc.contributor.authorMcMahon, Stephen A.
dc.contributor.authorLe Bas, Audrey
dc.contributor.authorSuits, Michael D. L.
dc.contributor.authorNaismith, James H.
dc.contributor.authorWhitfield, Chris
dc.date.accessioned2018-06-06T14:30:05Z
dc.date.available2018-06-06T14:30:05Z
dc.date.issued2018-05-22
dc.identifier253291301
dc.identifier99f7fc15-973c-481a-90a9-e95dae36f4b5
dc.identifier000432663000019
dc.identifier29735649
dc.identifier85047350859
dc.identifier000432663000019
dc.identifier.citationListon , S D , McMahon , S A , Le Bas , A , Suits , M D L , Naismith , J H & Whitfield , C 2018 , ' Periplasmic depolymerase provides insight into ABC transporter-dependent secretion of bacterial capsular polysaccharides ' , Proceedings of the National Academy of Sciences of the United States of America , vol. 115 , no. 21 , pp. E4870-E4879 . https://doi.org/10.1073/pnas.1801336115en
dc.identifier.issn0027-8424
dc.identifier.urihttps://hdl.handle.net/10023/13781
dc.descriptionThis work was supported in part by grants from the Canadian Institutes of Health Research (FDN_148364) (to C.W.). S.D.L. is a recipient of a Natural Science and Engineering Research Council Alexander Graham Bell Canada Graduate Scholarship and Michael Smith Foreign Study Supplement. C.W. is a Canada Research Chair. J.H.N. is a Wellcome Trust Investigator (100209/Z/12/Z).en
dc.description.abstractCapsules are surface layers of hydrated capsular polysaccharides (CPSs) produced by many bacteria. The human pathogen Salmonella enterica serovar Typhi produces "Vi antigen" CPS, which contributes to virulence. In a conserved strategy used by bacteria with diverse CPS structures, translocation of Vi antigen to the cell surface is driven by an ATP-binding cassette (ABC) transporter. These transporters are engaged in heterooligomeric complexes proposed to form an enclosed translocation conduit to the cell surface, allowing the transporter to power the entire process. We identified Vi antigen biosynthesis genetic loci in genera of the Burkholderiales, which are paradoxically distinguished from S. Typhi by encoding VexL, a predicted pectate lyase homolog. Biochemical analyses demonstrated that VexL is an unusual metal-independent endolyase with an acidic pH optimum that is specific for Oacetylated Vi antigen. A 1.22-Å crystal structure of the VexL-Vi antigen complex revealed features which distinguish common secreted catabolic pectate lyases from periplasmic VexL, which participates in cell-surface assembly. VexL possesses a right-handed parallel beta-superhelix, of which one face forms an electropositive glycan-binding groove with an extensive hydrogen bonding network that includes Vi antigen acetyl groups and confers substrate specificity. VexL provided a probe to interrogate conserved features of the ABC transporter-dependent export model. When introduced into S. Typhi, VexL localized to the periplasm and degraded Vi antigen. In contrast, a cytosolic derivative had no effect unless export was disrupted. These data provide evidence that CPS assembled in ABC transporter-dependent systems is actually exposed to the periplasm during envelope translocation.
dc.format.extent10
dc.format.extent1753382
dc.language.isoeng
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen
dc.subjectBacterial cell surfaceen
dc.subjectCapsular polysaccharideen
dc.subjectSalmonella entericaen
dc.subjectGlycosidaseen
dc.subjectGlycan exporten
dc.subjectQH301 Biologyen
dc.subjectDASen
dc.subject.lccQH301en
dc.titlePeriplasmic depolymerase provides insight into ABC transporter-dependent secretion of bacterial capsular polysaccharidesen
dc.typeJournal articleen
dc.contributor.sponsorThe Wellcome Trusten
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.contributor.institutionUniversity of St Andrews. School of Chemistryen
dc.contributor.institutionUniversity of St Andrews. EaSTCHEMen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.identifier.doi10.1073/pnas.1801336115
dc.description.statusPeer revieweden
dc.identifier.grantnumber100209/Z/12/Zen


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