Bioinformatics analysis of the MACPF superfamily

The Membrane Attack Complex/Perforin (MACPF) superfamily consists of a diverse group of proteins from three families involved in eukaryotic immunity, embryonic development, neural migration and bacterial pathogenesis. Characterization of the MACPF family involved recognition of possible orthology and horizontal gene transfer. Phylogenetic analysis of MACPF homologues using bioinformatics methods revealed a remarkably diverse range of proteins spanning both bacterial and eukaryotic kingdoms, with significant variations in the topological, hydrophobic and amphipathic characteristics of their sequences. The MACPF superfamily was expanded through the addition of the Cholesterol-Dependent Cytolysin (CDC) family. Comparison of the primary and tertiary structures of homologues from these two families revealed sequence similarity in the transmembrane regions of both families. Phylogenetic analysis demonstrated exclusive clustering of the CDC homologues, thereby identifying it as the second family within the MACPF superfamily. The third family to be included in the MACPF family was the Pleurotolysin (Pleurotolysin) family. Comparison of Pleurotolysin homologues from TCDB with the homologues obtained from the MACPF and CDC families revealed 15 pairs of proteins with comparison scores greater than 12 S.D. in their respective transmembrane domains. Addition of the pleurotolysin proteins to the phylogenetic tree containing MACPF and CDC homologues showed clustering of the majority of pleurotolysin

The Membrane Attack Complex/Perforin Superfamily.

The membrane attack complex/perforin (MACPF) superfamily consists of a diverse group of proteins involved in bacterial pathogenesis and sporulation as well as eukaryotic immunity, embryonic development, neural migration and fruiting body formation. The present work shows that the evolutionary relationships between the members of the superfamily, previously suggested by comparison of their tertiary structures, can also be supported by analyses of their primary structures. The superfamily includes the MACPF family (TC 1.C.39), the cholesterol-dependent cytolysin (CDC) family (TC 1.C.12.1 and 1.C.12.2) and the pleurotolysin pore-forming (pleurotolysin B) family (TC 1.C.97.1), as revealed by expansion of each family by comparison against a large protein database, and by the comparisons of their hidden Markov models. Clustering analyses demonstrated grouping of the CDC homologues separately from the 12 MACPF subfamilies, which also grouped separately from the pleurotolysin B family. Members of the MACPF superfamily revealed a remarkably diverse range of proteins spanning eukaryotic, bacterial, and archaeal taxonomic domains, with notable variations in protein domain architectures. Our strategy should also be helpful in putting together other highly divergent protein families