Rapid remodelling of the outer membrane proteome is essential for bacterial survival under fluctuating environmental conditions. We have found that during host-pathogen interactions, one of the important determinants for successful bacteria is the translocation and assembly module (TAM), which ensures the rapid deployment of a range of virulence factors. Using a functional assay, we have found that the folding rates of complex outer membrane proteins are inhibitively slower in the absence of the TAM.
The TAM itself is a membrane-spanning processing centre connecting the outer membrane to the inner membrane through the interaction of TamA and TamB. TamA has structural homology to the central component of the BAM complex, BamA, which is involved generally in outer membrane protein biogenesis. Using our assay, we have observed a dynamic interplay between these two nanomachines and found that when the TAM is absent, the BAM complex can facilitate assembly of complex proteins, albeit with low efficiency. By swapping the conserved domains of BamA and TamA, we observed that while the N-terminal POTRA domains were important for partner-protein interactions, the subtle differences in the transmembrane beta-barrel were required for substrate specificity.