The Membrane Attack Complex/Perforin Superfamily

J Mol Microbiol Biotechnol. 2017;27(4):252-267. doi: 10.1159/000481286. Epub 2017 Nov 17.


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.

Keywords: Bioinformatics; Cholesterol-dependent cytolysin; Membrane attack complex/perforin; Pleurotolysin; Pore formation; Superfamily; Toxin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bacteria / metabolism*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / classification
  • Bacterial Proteins / metabolism
  • Cholesterol / metabolism
  • Complement Membrane Attack Complex / chemistry*
  • Complement Membrane Attack Complex / classification*
  • Complement Membrane Attack Complex / metabolism
  • Fungal Proteins
  • Hemolysin Proteins
  • Models, Molecular
  • Perforin / chemistry*
  • Perforin / classification*
  • Perforin / metabolism
  • Protein Structure, Tertiary
  • Sequence Alignment


  • Bacterial Proteins
  • Complement Membrane Attack Complex
  • Fungal Proteins
  • Hemolysin Proteins
  • pleurotolysin B, oyster mushroom
  • Perforin
  • Cholesterol