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Published on: August 25, 2013
The Membrane Attack Complex/Perforin Superfamily
Gabriel Moreno-Hagelsieb1, Bennett Vitug, Arturo Medrano-Soto
1Department of Biology, Wilfrid Laurier University, Waterloo, ON, Canada.
Abstract:
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.
Insights
The membrane attack complex/perforin (MACPF) superfamily
Area of Science:
- Biochemistry
- Evolutionary Biology
- Structural Biology
Background:
- The membrane attack complex/perforin (MACPF) superfamily is a diverse protein group involved in various biological processes.
- Previous studies suggested evolutionary relationships based on tertiary structures.
Purpose of the Study:
- To investigate evolutionary relationships within the MACPF superfamily using primary structure analyses.
- To identify and classify members of the MACPF superfamily, including MACPF, CDC, and pleurotolysin B families.
Main Methods:
- Comparative analysis of protein primary structures.
- Expansion of protein families against a large database.
- Hidden Markov model comparisons.
- Clustering analyses.
Main Results:
- Evolutionary relationships within the MACPF superfamily are supported by primary structure analyses.
- The superfamily comprises the MACPF, cholesterol-dependent cytolysin (CDC), and pleurotolysin B families.
- Clustering analyses revealed distinct groupings for CDC, MACPF subfamilies, and pleurotolysin B.
- MACPF superfamily members are found across eukaryotic, bacterial, and archaeal domains with diverse architectures.
Conclusions:
- Primary structure analysis provides robust support for evolutionary relationships within the MACPF superfamily.
- The study clarifies the classification and evolutionary divergence of MACPF, CDC, and pleurotolysin B families.
- The developed strategy can aid in classifying other divergent protein families.
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