SUMMARY The outer-membrane of Gram-negative bacteria is critical for surface adhesion, pathogenicity, antibiotic resistance and survival. The major constituent – hydrophobic β-barrel O uter- M embrane P roteins (OMPs) – are 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 β- B arrel A ssembly M achinery (BAM) in the outer-membrane for insertion and folding. We show the H olo- T rans L ocon (HTL: an assembly of the protein-channel core-complex SecYEG, the ancillary sub-complex SecDF, and the membrane ‘insertase’ YidC) contacts SurA and BAM through periplasmic domains of SecDF and YidC, ensuring efficient OMP maturation. Our results show the trans-membrane proton-motive-force (PMF) acts at distinct stages of protein secretion: for SecA-driven translocation across the inner-membrane through SecYEG; and to communicate conformational changes via SecDF to the BAM machinery. The latter presumably ensures efficient passage of OMPs. These interactions provide insights of inter-membrane organisation, the importance of which is becoming increasingly apparent.

Inter-membrane association of the Sec and BAM translocons for bacterial outer-membrane biogenesis