Outer membrane protein evolution

Abstract

Outer membrane proteins have remarkably homogeneous structure. They are all up down β-barrels. Up down barrels themselves are composed of repeated sets of β-hairpins. The consistency of the usage of the β-hairpin throughout the outer membrane milieu allows for interrogation of the evolution of these repetitive structures. Here we describe recent investigations of outer membrane protein evolution and how evolutionary precepts have been used for novel outer membrane protein design.

Figure 1.. Evolution of OMBBs:

Most of the present day OMBBs evolved from an ancestral β-hairpin peptide. The ancestral peptide likely duplicated to become a four stranded multi-chain barrel then duplicated again to be an 8-stranded single chain barrel. This barrel is then the likely common ancestor to other higher number bacterial OMBB, which evolved in a distinct divergent pathway. The same ancestral peptide likely gave rise to the mitochondrial OMBB as well. Non-prototypical OMBBs like efflux pumps evolved through convergent evolution, although it is unclear if they arose from the same or different primordial beta hairpin.

Fig 2.. Various region of constrains in OMBBs.

A and B. A commonly studied bacterial OMBB, OmpA is shown in a tan ribbon. Inward residues are colored red, outward residues—blue, aromatic residues in the aromatic girdle—magenta, and the aromatic girdle region is highlighted with a pink box. In the background is the outer membrane bilayer with the phosphates that define the membrane border shown in orange spheres. Polar side chain interactions shown as green dotted lines. A. Side view, B. Top view, inset box showing Gly (cyan) and Tyr (red) in glycine rescue motif. C. Graph comparing differences in relative mutation rates as compared to the rates for surface residues which are defined as 1 [30,31,34]. The figure was prepared with the program PyMol using the PDB file 1QJP.