title: Two structural transitions in membrane pore formation by pneumolysin, the pore-forming toxin of Streptococcus pneumoniae.
abstract: The human pathogen Streptococcus pneumoniae produces soluble pneumolysin monomers that bind host cell membranes to form ring-shaped, oligomeric pores. We have determined three-dimensional structures of a helical oligomer of pneumolysin and of a membrane-bound ring form by cryo-electron microscopy. Fitting the four domains from the crystal structure of the closely related perfringolysin reveals major domain rotations during pore assembly. Oligomerization results in the expulsion of domain 3 from its original position in the monomer. However, domain 3 reassociates with the other domains in the membrane pore form. The base of domain 4 contacts the bilayer, possibly along with an extension of domain 3. These results reveal a two-stage mechanism for pore formation by the cholesterol-binding toxins.
authors.affiliation: Department of Biochemistry, University of Leicester, United Kingdom.
authors.forename: R J
authors.initials: RJ
authors.lastname: Gilbert
authors.forename: J L
authors.initials: JL
authors.lastname: Jiménez
authors.forename: S
authors.initials: S
authors.lastname: Chen
authors.forename: I J
authors.initials: IJ
authors.lastname: Tickle
authors.forename: J
authors.initials: J
authors.lastname: Rossjohn
authors.forename: M
authors.initials: M
authors.lastname: Parker
authors.forename: P W
authors.initials: PW
authors.lastname: Andrew
authors.forename: H R
authors.initials: HR
authors.lastname: Saibil
mesh_terms: D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000737:chemistry; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure*; D020285:Cryoelectron Microscopy; D003603:Cytotoxins / Q000737:chemistry; D006460:Hemolysin Proteins / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D008961:Models, Structural; D017433:Protein Structure, Secondary; D013296:Streptococcus pneumoniae / Q000502:physiology* / Q000648:ultrastructure*; D013301:Streptolysins / Q000737:chemistry*
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D003603:Cytotoxins; D006460:Hemolysin Proteins; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae; C020452:Clostridium perfringens theta-toxin