Evolutionary pathways of repeat protein topology in bacterial outer membrane proteins
Meghan Whitney Franklin,
Sergey Nepomnyachyi,
Ryan Feehan,
Nir Ben-Tal,
Rachel Kolodny,
Joanna SG Slusky
Affiliations
Meghan Whitney Franklin
Center for Computational Biology, University of Kansas, Kansas, United States
Sergey Nepomnyachyi
Department of Biochemistry and Molecular Biology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Israel; Department of Computer Science, University of Haifa, Haifa, Israel
Ryan Feehan
Center for Computational Biology, University of Kansas, Kansas, United States
Center for Computational Biology, University of Kansas, Kansas, United States; Department of Molecular Biosciences, University of Kansas, Kansas, United States
Outer membrane proteins (OMPs) are the proteins in the surface of Gram-negative bacteria. These proteins have diverse functions but a single topology: the β-barrel. Sequence analysis has suggested that this common fold is a β-hairpin repeat protein, and that amplification of the β-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.