title: Giant MACPF/CDC pore forming toxins: A class of their own.
abstract: Pore Forming Toxins (PFTs) represent a key mechanism for permitting the passage of proteins and small molecules across the lipid membrane. These proteins are typically produced as soluble monomers that self-assemble into ring-like oligomeric structures on the membrane surface. Following such assembly PFTs undergo a remarkable conformational change to insert into the lipid membrane. While many different protein families have independently evolved such ability, members of the Membrane Attack Complex PerForin/Cholesterol Dependent Cytolysin (MACPF/CDC) superfamily form distinctive giant β-barrel pores comprised of up to 50 monomers and up to 300Å in diameter. In this review we focus on recent advances in understanding the structure of these giant MACPF/CDC pores as well as the underlying molecular mechanisms leading to their formation. Commonalities and evolved variations of the pore forming mechanism across the superfamily are discussed. This article is part of a Special Issue entitled: Pore-Forming Toxins edited by Mauro Dalla Serra and Franco Gambale.
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Australia; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Melbourne, Australia.
authors.forename: Cyril F
authors.initials: CF
authors.lastname: Reboul
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Australia; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Melbourne, Australia.
authors.forename: James C
authors.initials: JC
authors.lastname: Whisstock
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Australia; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Melbourne, Australia; Department of Microbiology, Monash University, Melbourne, Australia.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Dunstone
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D019143:Evolution, Molecular; D006801:Humans; D054353:Perforin / Q000737:chemistry / Q000145:classification* / Q000378:metabolism*; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
chemical_list: D054353:Perforin
keywords: CDC; MACPF; Membrane Attack Complex; Perforin; Pleurotolysin; Pore forming toxin