Evolutionary pathways of repeat protein topology in bacterial outer membrane proteins

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

Research output: Contribution to journalArticlepeer-review


Outer membrane proteins (OMPs) are the proteins in the surface of Gram-negative bacteria. These proteins have diverse functions but a single topology: the b-barrel. Sequence analysis has suggested that this common fold is a b-hairpin repeat protein, and that amplification of the b-hairpin has resulted in 8–26-stranded barrels. Using an integrated approach that combines sequence and structural analyses, we find events in which non-amplification diversification also increases barrel strand number. Our network-based analysis reveals strand-number-based evolutionary pathways, including one that progresses from a primordial 8-stranded barrel to 16-strands and further, to 18-strands. Among these pathways are mechanisms of strand number accretion without domain duplication, like a loop-to-hairpin transition. These mechanisms illustrate perpetuation of repeat protein topology without genetic duplication, likely induced by the hydrophobic membrane. Finally, we find that the evolutionary trace is particularly prominent in the C-terminal half of OMPs, implicating this region in the nucleation of OMP folding.

Original languageEnglish
Article numbere40308
StatePublished - 1 Nov 2018

Bibliographical note

Publisher Copyright:
© Franklin et al.

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology
  • General Neuroscience


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