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

Meghan Whitney Franklin, Sergey Nepomnyachiy, Ryan Feehan, Nir Ben-Tal, Rachel Kolodny, Joanna S.G. Slusky*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


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. Although most outer membrane β-barrels (OMBBs) are related, Franklin et al. use sequences and structures to suggest that efflux-OMBBs are unrelated to other OMBBs. This leaves the prototypical-related autotransporters as the best models of primordial OMBB structure. Moreover, the efflux-OMBBs align with the periplasmic regions of efflux pumps, creating a structural palindrome.

Original languageEnglish
Pages (from-to)1266-1274.e2
Issue number9
StatePublished - 4 Sep 2018


FundersFunder number
National Science FoundationMCB160205
National Institutes of HealthDP2GM128201, P20GM103418, T32-GM008359
National Institute of General Medical SciencesP20GM113117
Israel Science Foundation450/16
National Science Foundation


    • CyToStruct
    • Cytoscape
    • beta barrels
    • convergent evolution
    • efflux pumps
    • molecular evolution
    • outer membrane proteins
    • primordial beta barrel
    • sequence analysis
    • structure analysis


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