Fig. 6: Proposed model of SurA-mediated delivery of OMPs to BAM for folding.

In the membrane, BAM is in dynamic equilibrium, populating a number of conformations including those in which the BamA barrel is in either a ‘lateral-open’ or ‘lateral-closed’ conformation (top). SurA is also dynamic, populating ‘Core-P1 open’ and ‘Core-P1 closed’ ensembles of states (bottom). The P2 domain is shown residing close to the core domain in solution (‘Core-P2 closed’). OMPs bind in a cradle formed by the Core and P1 domains, with binding sites primarily located on the core domain^30,31. OMP binding to SurA causes the OMP to populate expanded states^31,34,35 The OMP–SurA complex binds to BAM, to form an OMP–SurA–BAM ternary complex, resulting in conformational changes in both SurA (opening of the P1 and P2 domains) and BAM (favouring the lateral-closed state, which we propose to be the OMP acceptor state). The OMP binding cradle of SurA is oriented into the BAM periplasmic ring, allowing release of the unfolded OMP into a protective ‘chaperonin-like’ environment⁵, and presentation of the OMP to the BamA β-barrel for folding in a C- to N-terminus direction via β-strand elongation from β1 of the BamA barrel^{5,52,53,59,61,114}. Here, a single β-hairpin of the substrate is depicted bound to β1 of the BamA barrel, however more extensive β-sheet structure in the substrate may begin to form in the periplasm (or at the water–membrane interface) prior to membrane integration^5,53,114,115, in a manner analogous to a seeded amyloid aggregation reaction^5,116,117.