title: The membrane attack complex, perforin and cholesterol-dependent cytolysin superfamily of pore-forming proteins.
abstract: The membrane attack complex and perforin proteins (MACPFs) and bacterial cholesterol-dependent cytolysins (CDCs) are two branches of a large and diverse superfamily of pore-forming proteins that function in immunity and pathogenesis. During pore formation, soluble monomers assemble into large transmembrane pores through conformational transitions that involve extrusion and refolding of two α-helical regions into transmembrane β-hairpins. These transitions entail a dramatic refolding of the protein structure, and the resulting assemblies create large holes in cellular membranes, but they do not use any external source of energy. Structures of the membrane-bound assemblies are required to mechanistically understand and modulate these processes. In this Commentary, we discuss recent advances in the understanding of assembly mechanisms and molecular details of the conformational changes that occur during MACPF and CDC pore formation.
authors.affiliation: Department of Crystallography/Biological Sciences, Institute of Structural and Molecular Biology, Birkbeck College, London WC1E 7HX, UK.
authors.forename: Natalya
authors.initials: N
authors.lastname: Lukoyanova
authors.affiliation: London Centre for Nanotechnology, University College London, London WC1H 0AH, UK Department of Physics and Astronomy, University College London, London WC1E 6BT, UK.
authors.forename: Bart W
authors.initials: BW
authors.lastname: Hoogenboom
authors.affiliation: Department of Crystallography/Biological Sciences, Institute of Structural and Molecular Biology, Birkbeck College, London WC1E 7HX, UK h.saibil@mail.cryst.bbk.ac.uk.
authors.forename: Helen R
authors.identifier: 0000-0002-2266-8891
authors.initials: HR
authors.lastname: Saibil
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D015938:Complement Membrane Attack Complex / Q000737:chemistry / Q000378:metabolism*; D003603:Cytotoxins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000378:metabolism; D054353:Perforin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D015938:Complement Membrane Attack Complex; D003603:Cytotoxins; D046912:Multiprotein Complexes; D054353:Perforin; D002784:Cholesterol
keywords: CDC; MACPF; Pore-forming proteins