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Dynamics of an LPS translocon induced by substrate and an antimicrobial peptide
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Fiorentino, Francesco, Sauer, Joshua B., Qiu, XingYu, Corey, Robin A., Cassidy, Keith, Mynors-Wallis, Benjamin, Mehmood, Shahid, Bolla, Jani R., Stansfeld, Phillip J. and Robinson, Carol V. (2020) Dynamics of an LPS translocon induced by substrate and an antimicrobial peptide. Nature Chemical Biology, 17 . pp. 187-195. doi:10.1038/s41589-020-00694-2 ISSN 1552-4450.
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Official URL: https://doi.org/10.1038/s41589-020-00694-2
Abstract
Lipopolysaccharide (LPS) transport to the outer membrane (OM) is a crucial step in the biogenesis of microbial surface defenses. Although many features of the translocation mechanism have been elucidated, molecular details of LPS insertion via the LPS transport (Lpt) OM protein LptDE remain elusive. Here, we integrate native MS with hydrogen–deuterium exchange MS and molecular dynamics simulations to investigate the influence of substrate and peptide binding on the conformational dynamics of LptDE. Our data reveal that LPS induces opening of the LptD β-taco domain, coupled with conformational changes on β-strands adjacent to the putative lateral exit gate. Conversely, an antimicrobial peptide, thanatin, stabilizes the β-taco, thereby preventing LPS transport. Our results illustrate that LPS insertion into the OM relies on concerted opening movements of both the β-barrel and β-taco domains of LptD, and suggest a means for developing antimicrobial therapeutics targeting this essential process in Gram-negative ESKAPE pathogens.
Item Type: | Journal Article | |||||||||||||||||||||||||||||||||||||||
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Subjects: | Q Science > QP Physiology R Medicine > RS Pharmacy and materia medica |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | |||||||||||||||||||||||||||||||||||||||
Library of Congress Subject Headings (LCSH): | Endotoxins , Gram-negative bacteria, Peptide antibiotics | |||||||||||||||||||||||||||||||||||||||
Journal or Publication Title: | Nature Chemical Biology | |||||||||||||||||||||||||||||||||||||||
Publisher: | Nature Publishing Group | |||||||||||||||||||||||||||||||||||||||
ISSN: | 1552-4450 | |||||||||||||||||||||||||||||||||||||||
Official Date: | 16 November 2020 | |||||||||||||||||||||||||||||||||||||||
Dates: |
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Volume: | 17 | |||||||||||||||||||||||||||||||||||||||
Page Range: | pp. 187-195 | |||||||||||||||||||||||||||||||||||||||
DOI: | 10.1038/s41589-020-00694-2 | |||||||||||||||||||||||||||||||||||||||
Status: | Peer Reviewed | |||||||||||||||||||||||||||||||||||||||
Publication Status: | Published | |||||||||||||||||||||||||||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||||||||||||||||||||||||||
Date of first compliant deposit: | 21 October 2020 | |||||||||||||||||||||||||||||||||||||||
Date of first compliant Open Access: | 16 May 2021 | |||||||||||||||||||||||||||||||||||||||
RIOXX Funder/Project Grant: |
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