Outer membrane protein assembly mediated by BAM-SurA complexes
The outer membrane is a formidable barrier that protects Gram-negative bacteria against environmental threats. Its integrity requires the correct folding and insertion of outer membrane proteins (OMPs) by the membrane-embedded β-barrel assembly machinery (BAM). Unfolded OMPs are delivered to BAM by the periplasmic chaperone SurA, but how SurA and BAM work together to ensure successful OMP delivery and folding remains unclear. Here, guided by AlphaFold2 models, we use disulphide bond engineering in an attempt to trap SurA in the act of OMP delivery to BAM, and solve cryoEM structures of a series of complexes. The results suggest that SurA binds BAM at its soluble POTRA-1 domain, which may trigger conformational changes in both BAM and SurA that enable transfer of the unfolded OMP to the BAM lateral gate for insertion into the outer membrane. Mutations that disrupt the interaction between BAM and SurA result in outer membrane assembly defects, supporting the key role of SurA in outer membrane biogenesis.
Authors
- Neil A. Ranson (ORCID: https://orcid.org/0000-0002-3640-5275)
- Jim E. Horne (ORCID: https://orcid.org/0000-0001-5260-2634)
- Romany J. Horne (ORCID: https://orcid.org/0000-0001-9711-7691)
- Antonio N. Calabrese (ORCID: https://orcid.org/0000-0003-2437-7761)
- Till F. Schäberle (ORCID: https://orcid.org/0000-0001-9947-8079)
- Nils Böhringer (ORCID: https://orcid.org/0009-0000-0673-4820)
- Sheena E. Radford (ORCID: https://orcid.org/0000-0002-3079-8039)
- Joel A. Crossley (ORCID: https://orcid.org/0000-0002-6656-1578)
- Katherine Fenn
Institutions
- University of Leeds (GB)
- Justus-Liebig-Universität Gießen (DE)
- Granta Design (United Kingdom) (GB)
- German Center for Infection Research (DE)
- Fraunhofer Institute for Molecular Biology and Applied Ecology (DE)
- Lawn Tennis Association (GB)
- Institute of Structural and Molecular Biology (GB)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-09-01
- DOI
- https://doi.org/10.1038/s41467-024-51358-x
- Citations
- 27
- Primary Topic
- Bacterial Genetics and Biotechnology
- Type
- article
- Field-Weighted Citation Impact
- 14.86
Funders
- Wellcome
- Université Catholique de Louvain
- Deutsches Zentrum für Infektionsforschung
- University of Leeds
- Bundesministerium für Bildung und Forschung
- National Institutes of Health
- Medical Research Council
- Biotechnology and Biological Sciences Research Council