Dynamics of an LPS translocon induced by substrate and an antimicrobial peptide.

Nature Chemical Biology
Francesco FiorentinoCarol V Robinson

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.

References

Feb 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·P FehlbaumJ A Hoffmann
Feb 16, 2006·Journal of Lipid Research·Christian R H RaetzEdward A Dennis
Aug 26, 2006·Journal of the American Society for Mass Spectrometry·David D WeisIgnatius J Kass
Jan 11, 2007·The Journal of Chemical Physics·Giovanni BussiMichele Parrinello
Apr 5, 2007·Nature Protocols·Helena Hernández, Carol V Robinson
Jul 28, 2009·Nature Reviews. Microbiology·Natividad RuizThomas J Silhavy
Feb 20, 2010·Science·Nityakalyani SrinivasJohn A Robinson
Mar 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Shu-Sin ChngDaniel Kahne
Dec 22, 2010·Chemical Society Reviews·Lars KonermannYu-Hong Liu
Jan 25, 2011·Proceedings of the National Academy of Sciences of the United States of America·Elizaveta FreinkmanDaniel Kahne
Apr 19, 2011·Journal of Computational Chemistry·Naveen Michaud-AgrawalOliver Beckstein
Jul 19, 2012·Chembiochem : a European Journal of Chemical Biology·Martina WerneburgJohn A Robinson
Mar 9, 2013·Nature Protocols·Arthur LaganowskyCarol V Robinson
Sep 11, 2013·Journal of the American Society for Mass Spectrometry·Miklos GuttmanKelly K Lee
Mar 4, 2014·Annual Review of Biochemistry·Chris Whitfield, M Stephen Trent
Apr 23, 2014·Nucleic Acids Research·Xavier Robert, Patrice Gouet
Jul 6, 2014·Nature·Haohao DongChangjiang Dong
Oct 29, 2014·Proceedings of the National Academy of Sciences of the United States of America·John J SkinnerTobin R Sosnick
Jun 20, 2015·Journal of Chemical Theory and Computation·Elizabeth JefferysPhilip W Fowler
Jul 22, 2015·Proceedings of the National Academy of Sciences of the United States of America·Filip Persson, Bertil Halle
Nov 18, 2015·Journal of Chemical Theory and Computation·Tsjerk A WassenaarSiewert J Marrink
Apr 12, 2011·Journal of Chemical Theory and Computation·Phillip J Stansfeld, Mark S P Sansom
May 1, 2008·Journal of Chemical Theory and Computation·Luca MonticelliSiewert-Jan Marrink
Jan 27, 2016·Journal of the American Society for Mass Spectrometry·Miklos GuttmanKelly K Lee
Mar 31, 2016·Nature Reviews. Microbiology·Suguru OkudaDaniel Kahne
Jan 11, 2017·Nature Communications·Michael LandrehCarol V Robinson
Apr 11, 2017·Nature Structural & Molecular Biology·Qingshan LuoYihua Huang
Aug 16, 2017·Proceedings of the National Academy of Sciences of the United States of America·Jieyu ZhouFrank Jordan
Feb 21, 2018·Nature Chemistry·Jani Reddy BollaCarol V Robinson
May 15, 2018·Science Advances·Patrick S MerkleKasper D Rand
Sep 27, 2018·Journal of the American Chemical Society·Ran XieDaniel Kahne
Oct 10, 2018·Nature Communications·Chloe MartensArgyris Politis
Nov 6, 2018·Nucleic Acids Research·Yasset Perez-RiverolJuan Antonio Vizcaíno

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Citations

Apr 3, 2021·Drug Discovery Today·Scott S Walker, Todd A Black
May 9, 2021·Current Opinion in Structural Biology·Jani R BollaCarol V Robinson
Jul 3, 2021·Journal of Medicinal Chemistry·Francesco FiorentinoDante Rotili
Sep 30, 2021·Chemical Communications : Chem Comm·Francesco FiorentinoCarol V Robinson

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Methods Mentioned

BETA
X-ray
crosslinking studies
size-exclusion chromatography

Software Mentioned

ESPript
NPS
Martinize Python script
Protein Lynx Global Server
GROMACS
HX
UniDec
MDAnalysis
GraphPad Prism
TopMatch

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