Efflux Pumps Represent Possible Evolutionary Convergence onto the β-Barrel Fold

There are around 100 varieties of outer membrane proteins in each Gram-negative bacteria. All of these proteins have the same fold-an up-down β-barrel. It has been suggested that all membrane β-barrels excluding lysins are homologous. Here we suggest that β-barrels of efflux pumps have converged on this fold as well. By grouping structurally solved outer membrane β-barrels (OMBBs) by sequence we find that the membrane environment may have led to convergent evolution of the barrel fold. Specifically, the lack of sequence linkage to other barrels coupled with distinctive structural differences, such as differences in strand tilt and barrel radius, suggest that the outer membrane factor of efflux pumps evolutionarily converged on the barrel. Rather than being related to other OMBBs, sequence and structural similarity in the periplasmic region of the outer membrane factor of efflux pumps suggests an evolutionary link to the periplasmic subunit of the same pump complex.