Proteins in the outer membrane of gram-negative cell envelopes are characterized by the membrane-embedded beta-barrel domain, and their correct folding and insertion into the lipid bilayer is mediated by the beta-barrel assembly machinery (BAM). The essential core protein of this complex is BamA, a member of the Omp85 protein superfamily working in a chaperone-like fashion. Members of the Omp85 protein superfamily are characterized by a shared barrel domain and a variable number of polypeptide-transport associated (POTRA) domains, which reach into the periplasm. In addition to BamA there are now examples of Omp85 sub- and neofunctionalisation: TamA, an Omp85 protein found in Proteobacteria in addition to BamA, is the core component of the TAM complex which assists BAM in the correct folding of a group of autotransporters; and another Omp85 protein has an additional lipase domain associated (patatin-like), which becomes exposed to the extracellular space, likely functioning as virulence factor.
This study addresses the diversity of the Omp85 proteins at domain architecture as well as sequence level. We furthermore performed phylogenetic analyses investigating the evolutionary history of this essential family of membrane chaperones. Our large-scale computational analysis identified several new domain architectures differing from the classic barrel + POTRA structure, as well as at least five different subgroups of the classical domain profile, indicating a far wider variety of membrane-embedded chaperone-like proteins like BamA and TamA. Phylogenetic analyses and similarity networks revealed this family to be highly dynamic with respect to different numbers of paralogues, different subfamilies of similar domain architectures, and different domain architectures. Correlating this to the respective bacterial organisms revealed enrichment in organisms thriving in highly variable environments, indicating that additional Omp85 proteins might facilitate a more diverse membrane proteome potentially important for interactions with the environment.