Evolution of Environmentally-Enforced, Repeat Protein Topology in the Outer Membrane

Abstract

Outer membrane beta barrels (OMBBs) are the proteins on the surface of Gram negative bacteria. These proteins have diverse functions but only a single topology, the beta barrel. It has been suggested that this common fold is a repeat protein with the repeating unit of a beta hairpin. By grouping structurally solved OMBBs by sequence, a detailed evolutionary story unfolds. A strand-number based pathway manifests with progression from a primordial 8-stranded barrel to 16-stranded and then to 18-stranded barrels. The transitions from 16- to 18-stranded barrels show mechanisms of strand number variation without domain duplication, such as a loop to hairpin transition. This indicates that repeat protein topology can be perpetuated without genetic duplication likely because the topology is being enforced by the membrane environment. Moreover, we find the evolutionary trace is particularly prominent in the C-terminal half of OMBBs which may be relevant to understanding OMBB folding pathways.