Inter-membrane association of the Sec and BAM translocons for bacterial outer-membrane biogenesis
Abstract
The outer-membrane of Gram-negative bacteria is critical for surface adhesion, pathogenicity, antibiotic resistance and survival. The major constituent – hydrophobic b-barrel Outer-Membrane Proteins (OMPs) – are first secreted across the inner-membrane through the Sec-translocon for delivery to periplasmic chaperones e.g. SurA, which prevent aggregation. OMPs are then offloaded to the b-Barrel Assembly Machinery (BAM) in the outer-membrane for insertion and folding. We show the Holo-TransLocon (HTL) – an assembly of the protein-channel core-complex SecYEG, the ancillary sub-complex SecDF, and the membrane 'insertase' YidC – contacts BAM through periplasmic domains of SecDF and YidC, ensuring efficient OMP maturation. Furthermore, the proton-motive-force (PMF) across the inner-membrane acts at distinct stages of protein secretion: (1) SecA-driven translocation through SecYEG; and (2) communication of conformational changes via SecDF across the periplasm to BAM. The latter presumably drives efficient passage of OMPs. These interactions provide insights of inter-membrane organisation and communication, the importance of which is becoming increasingly apparent.
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All data generated or analysed during this study are included in the manuscript and supplementary information. Information regarding statistical testing is located in materials and methods and corresponding figure legends.
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Funding
Biotechnology and Biological Sciences Research Council (BB/S008349/1)
- Sara Alvira
EMBO (LTFCOFUND2013)
- Sara Alvira
EMBO (GA-2013-609409)
- Sara Alvira
Biotechnology and Biological Sciences Research Council (BB/S008349/1)
- Daniel W Watkins
Biotechnology and Biological Sciences Research Council (BB/S008349/1)
- Ian Collinson
Biotechnology and Biological Sciences Research Council (BB/N015126/1)
- Ian Collinson
Biotechnology and Biological Sciences Research Council (BB/N015126/1)
- Daniel W Watkins
Biotechnology and Biological Sciences Research Council (BB/M003604/1)
- Ian Collinson
Biotechnology and Biological Sciences Research Council (BB/M003604/1)
- Sara Alvira
Biotechnology and Biological Sciences Research Council (BB/J014400/1)
- Luca A Troman
EMBO (ALTF 710-2015)
- Sara Alvira
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Alvira et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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