Structural insight into tight junction disassembly by Clostridium perfringens enterotoxin

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Science  13 Feb 2015:
Vol. 347, Issue 6223, pp. 775-778
DOI: 10.1126/science.1261833

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How a toxin makes epithelial sheets leaky

The entire human body and its many compartments are shielded from their external environments by the barrier function of epithelial cell sheets. The paracellular barrier function of tight junctions (TJs) is critical for maintaining homeostasis in any multicellular organism, especially in the skin and internal organs and at the blood-brain barrier. One of the major components of TJs is a family of adhesive membrane proteins known as claudins. Several members of the claudin family are receptors for the bacterial toxin Clostridium perfringens enterotoxin. This toxin often causes food-borne illness both in humans and animals. Saitoh et al. crystallized a complex between the toxin and a claudin that reveals just how the toxin damages epithelial barriers (see the Perspective by Artursson and Knight).

Science, this issue p. 775; see also p. 716


The C-terminal region of Clostridium perfringens enterotoxin (C-CPE) can bind to specific claudins, resulting in the disintegration of tight junctions (TJs) and an increase in the paracellular permeability across epithelial cell sheets. Here we present the structure of mammalian claudin-19 in complex with C-CPE at 3.7 Å resolution. The structure shows that C-CPE forms extensive hydrophobic and hydrophilic interactions with the two extracellular segments of claudin-19. The claudin-19/C-CPE complex shows no density of a short extracellular helix that is critical for claudins to assemble into TJ strands. The helix displacement may thus underlie C-CPE–mediated disassembly of TJs.

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