title: Structural features of cholesterol dependent cytolysins and comparison to other MACPF-domain containing proteins.
abstract: Five different cholesterol-dependent cytolysins (CDCs) have now had their atomic structures solved. Here their structures are compared and shown to vary less in the C-terminal region than they do in their N-terminal MACPF/CDC homology region. The most variable region of the C-terminal domain is the undecapeptide, which is observed in two clusters of conformations, and comparison of this domain with the C2 domain of perforin shows that the two structures have a common ancestor. Structural studies of CDC pre-pore and pore oligomers by cryo-electron microscopy and atomic force microscopy have revealed much about their mechanism of action. Understanding the activity of CDCs has required a combination of structural, biophysical and functional assays but current models of pore formation still require development to account for variable functional pore size.
authors.affiliation: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK, gilbert@strubi.ox.ac.uk.
authors.forename: Robert
authors.initials: R
authors.lastname: Gilbert
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism*; D015938:Complement Membrane Attack Complex / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D003603:Cytotoxins / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D054353:Perforin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D058105:Polymerization; D011487:Protein Conformation
chemical_list: D015938:Complement Membrane Attack Complex; D003603:Cytotoxins; D054353:Perforin; D002784:Cholesterol