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dc.contributor.authorGu, Y.
dc.contributor.authorStansfeld, P.
dc.contributor.authorZeng, Y.
dc.contributor.authorDong, H.
dc.contributor.authorWang, W.
dc.contributor.authorDong, C.
dc.date.accessioned2015-03-04T11:31:02Z
dc.date.available2015-03-04T11:31:02Z
dc.date.issued2015-03-03
dc.identifier.citationGu , Y , Stansfeld , P , Zeng , Y , Dong , H , Wang , W & Dong , C 2015 , ' Lipopolysaccharide is inserted into the outer membrane through an intramembrane hole, a lumen gate, and the lateral opening of LptD ' , Structure , vol. 23 , no. 3 , pp. 496-504 . https://doi.org/10.1016/j.str.2015.01.001en
dc.identifier.issn0969-2126
dc.identifier.otherPURE: 172486467
dc.identifier.otherPURE UUID: cf3205e1-8e18-4696-8606-393eac7864ec
dc.identifier.otherWOS: 000350886100009
dc.identifier.otherPubMed: 25684578
dc.identifier.otherScopus: 84923880501
dc.identifier.urihttp://hdl.handle.net/10023/6172
dc.descriptionC.D. is a recipient of the Wellcome Trust New Investigator Award. P.J.S. is supported by BBSRC grant BB/I019855/1 and W.W. is supported by China Natural Science Foundation of Guangdong Province grant (S2013010016539). Date of Acceptance: 06/01/2015en
dc.description.abstractLipopolysaccharide (LPS) is essential for the vitality of most Gram-negative bacteria and plays an important role in bacterial multidrug resistance. The LptD/E translocon inserts LPS into the outer leaflet, the mechanism of which is poorly understood. Here, we report mutagenesis, functional assays, and molecular dynamics simulations of the LptD/E complex, which suggest two distinct pathways for the insertion of LPS. The N-terminal domain of LptD comprises a hydrophobic slide that injects the acyl tails of LPS directly into the outer membrane through an intramembrane hole, while the core oligosaccharide and O-antigen pass a lumen gate that triggers the unzipping of the lateral opening between strands β1C and β26C of the barrel of LptD, to finalize LPS insertion. Mutation of the LPS transport related residues or block of the LPS transport pathways results in the deaths of Escherichia coli. These findings are important for the development of novel antibiotics. Through molecular dynamics simulations, mutagenesis, and functional assays, Gu etal. reveal key residues of the N-terminal domain, a hydrophobic intramembrane hole, and a luminal gate of LptD for LPS transport, insertion, and translocation. These findings are significant not just for understanding the function of LptD, but also to develop novel antibiotics.
dc.language.isoeng
dc.relation.ispartofStructureen
dc.rightsCopyright, the Authors 2015. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).en
dc.subjectQD Chemistryen
dc.subjectNDASen
dc.subject.lccQDen
dc.titleLipopolysaccharide is inserted into the outer membrane through an intramembrane hole, a lumen gate, and the lateral opening of LptDen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Chemistryen
dc.identifier.doihttps://doi.org/10.1016/j.str.2015.01.001
dc.description.statusPeer revieweden
dc.identifier.urlhttp://www.sciencedirect.com/science/article/pii/S0969212615000027#appd002en


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