Crystal structure of Clostridium perfringens enterotoxin displays features of beta-pore-forming toxins

J Biol Chem. 2011 Jun 3;286(22):19549-55. doi: 10.1074/jbc.M111.228478. Epub 2011 Apr 12.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Clostridium perfringens / chemistry*
  • Clostridium perfringens / genetics
  • Crystallography, X-Ray
  • Enterotoxins / chemistry*
  • Enterotoxins / genetics
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Structure-Activity Relationship

Substances

  • Enterotoxins
  • enterotoxin, Clostridium

Associated data

  • PDB/3AM2