Darobactin B Stabilises a Lateral-Closed Conformation of the BAM Complex in E. coli Cells.


Journal

Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543

Informations de publication

Date de publication:
21 08 2023
Historique:
received: 19 12 2022
medline: 18 8 2023
pubmed: 10 5 2023
entrez: 10 5 2023
Statut: ppublish

Résumé

The β-barrel assembly machinery (BAM complex) is essential for outer membrane protein (OMP) folding in Gram-negative bacteria, and represents a promising antimicrobial target. Several conformational states of BAM have been reported, but all have been obtained under conditions which lack the unique features and complexity of the outer membrane (OM). Here, we use Pulsed Electron-Electron Double Resonance (PELDOR, or DEER) spectroscopy distance measurements to interrogate the conformational ensemble of the BAM complex in E. coli cells. We show that BAM adopts a broad ensemble of conformations in the OM, while in the presence of the antibiotic darobactin B (DAR-B), BAM's conformational equilibrium shifts to a restricted ensemble consistent with the lateral closed state. Our in-cell PELDOR findings are supported by new cryoEM structures of BAM in the presence and absence of DAR-B. This work demonstrates the utility of PELDOR to map conformational changes in BAM within its native cellular environment.

Identifiants

pubmed: 37162386
doi: 10.1002/anie.202218783
doi:

Substances chimiques

Escherichia coli Proteins 0
darobactin 0
Bacterial Outer Membrane Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e202218783

Subventions

Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/S018069/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/W019795/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/M011151/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P018491/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 108466/Z/15/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 221524/Z/20/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 222373/Z/21/Z
Pays : United Kingdom

Informations de copyright

© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.

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Auteurs

Samuel F Haysom (SF)

Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, University of Leeds, Leeds, LS2 9JT, UK.

Jonathan Machin (J)

Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, University of Leeds, Leeds, LS2 9JT, UK.

James M Whitehouse (JM)

Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, University of Leeds, Leeds, LS2 9JT, UK.

Jim E Horne (JE)

Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, University of Leeds, Leeds, LS2 9JT, UK.

Katherine Fenn (K)

Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, University of Leeds, Leeds, LS2 9JT, UK.

Yue Ma (Y)

Astbury Centre for Structural Molecular Biology, School of Biomedical Sciences, University of Leeds, Leeds, LS2 9JT, UK.
School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic and Health Science Centre, The University of Manchester, Manchester, M13 9PT, UK.
Manchester Institute of Biotechnology, The University of Manchester, Manchester, M1 7DN, UK.

Hassane El Mkami (H)

School of Physics and Astronomy, University of St. Andrews, St. Andrews, KY16 9SS, UK.

Nils Böhringer (N)

Institute for Insect Biotechnology, Natural Product Research, Justus-Liebig-University Giessen, Ohlebergsweg 12, 35392, Giessen, Germany.
German Center for Infection Research (DZIF), Partner Site Giessen-Marburg-Langen, Ohlebergsweg 12, 35392, Giessen, Germany.

Till F Schäberle (TF)

Institute for Insect Biotechnology, Natural Product Research, Justus-Liebig-University Giessen, Ohlebergsweg 12, 35392, Giessen, Germany.
German Center for Infection Research (DZIF), Partner Site Giessen-Marburg-Langen, Ohlebergsweg 12, 35392, Giessen, Germany.
Natural Product Department, Fraunhofer-Institute for Molecular Biology and Applied Ecology (IME), Ohlebergsweg 12, 35392, Giessen, Germany.

Neil A Ranson (NA)

Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, University of Leeds, Leeds, LS2 9JT, UK.

Sheena E Radford (SE)

Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, University of Leeds, Leeds, LS2 9JT, UK.

Christos Pliotas (C)

Astbury Centre for Structural Molecular Biology, School of Biomedical Sciences, University of Leeds, Leeds, LS2 9JT, UK.
School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic and Health Science Centre, The University of Manchester, Manchester, M13 9PT, UK.
Manchester Institute of Biotechnology, The University of Manchester, Manchester, M1 7DN, UK.

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Classifications MeSH