UC San Diego

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 pleurotolysins