title: Crystal structure of Clostridium perfringens enterotoxin displays features of beta-pore-forming toxins.
abstract: Clostridium perfringens enterotoxin (CPE) is a cause of food poisoning and is considered a pore-forming toxin, which damages target cells by disrupting the selective permeability of the plasma membrane. However, the pore-forming mechanism and the structural characteristics of the pores are not well documented. Here, we present the structure of CPE determined by x-ray crystallography at 2.0 Å. The overall structure of CPE displays an elongated shape, composed of three distinct domains, I, II, and III. Domain I corresponds to the region that was formerly referred to as C-CPE, which is responsible for binding to the specific receptor claudin. Domains II and III comprise a characteristic module, which resembles those of β-pore-forming toxins such as aerolysin, C. perfringens ε-toxin, and Laetiporus sulfureus hemolytic pore-forming lectin. The module is mainly made up of β-strands, two of which span its entire length. Domain II and domain III have three short β-strands each, by which they are distinguished. In addition, domain II has an α-helix lying on the β-strands. The sequence of amino acids composing the α-helix and preceding β-strand demonstrates an alternating pattern of hydrophobic residues that is characteristic of transmembrane domains forming β-barrel-made pores. These structural features imply that CPE is a β-pore-forming toxin. We also hypothesize that the transmembrane domain is inserted into the membrane upon the buckling of the two long β-strands spanning the module, a mechanism analogous to that of the cholesterol-dependent cytolysins.
authors.affiliation: Graduate School of Science and Technology, Department of Biomolecular Engineering, Kyoto Institute of Technology, Sakyo-ku, Kyoto, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Kitadokoro
authors.forename: Kousuke
authors.initials: K
authors.lastname: Nishimura
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kamitani
authors.forename: Aya
authors.initials: A
authors.lastname: Fukui-Miyazaki
authors.forename: Hirono
authors.initials: H
authors.lastname: Toshima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Abe
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kamata
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Sugita-Konishi
authors.forename: Shigeki
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Hajime
authors.initials: H
authors.lastname: Karatani
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Horiguchi
mesh_terms: D003016:Clostridium perfringens / Q000737:chemistry* / Q000235:genetics; D018360:Crystallography, X-Ray; D004768:Enterotoxins / Q000737:chemistry* / Q000235:genetics; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D004768:Enterotoxins; C035598:enterotoxin, Clostridium