Dynamic interplay between the periplasmic chaperone SurA and the BAM complex in outer membrane protein folding

Correct folding of outer membrane proteins (OMPs) into the outer membrane of Gram-negative bacteria depends on delivery of unfolded OMPs to the beta-barrel assembly machinery (BAM). How unfolded substrates are presented to BAM remains elusive, but the major OMP chaperone SurA is proposed to play a key role. Here, we have used hydrogen deuterium exchange mass spectrometry (HDX-MS), crosslinking, in vitro folding and binding assays and computational modelling to show that the core domain of SurA and one of its two PPIase domains are key to the SurA-BAM interaction and are required for maximal catalysis of OMP folding. We reveal that binding causes changes in BAM and SurA conformation and/or dynamics distal to the sites of binding, including at the BamA beta 1-beta 16 seam. We propose a model for OMP biogenesis in which SurA plays a crucial role in OMP delivery and primes BAM to accept substrates for folding. Interaction of the outer membrane protein (OMP) chaperone SurA and the OMP folding catalyst BAM results in changes in the conformational ensembles of both species, suggesting a mechanism for delivery of OMPs to BAM in Gram-negative bacteria.