The carboxy‐terminal C 2 ‐like domain of the α‐toxin from Clostridium perfringens mediates calcium‐dependent membrane recognition - Archive ouverte HAL Access content directly
Journal Articles Molecular Microbiology Year : 2003

The carboxy‐terminal C 2 ‐like domain of the α‐toxin from Clostridium perfringens mediates calcium‐dependent membrane recognition

Abstract

The lethal, cytolytic alpha-toxin (phospholipase C) of Clostridium perfringens consists of two distinct modules: the larger N-terminal domain catalyses phospholipid hydrolysis, and its activity is potentiated by a smaller C-terminal domain. Calcium ions are essential for the binding of alpha-toxin to lipid films. Sixteen alpha-toxin variants with single amino acid substitutions in the C-terminal region were obtained using site-directed mutagenesis and T7 expression technology. Five of these variants showed reduced phospholipase C activity and were considerably less active than native alpha-toxin under calcium-limiting conditions. Replacement of Thr-272 by Pro diminished phospholipase C activity, severely affected haemolysis and platelet aggregation and perturbed a surface-exposed conformational epitope. The results of sequence comparisons and molecular modelling indicate that the C-terminal region probably belongs to the growing family of C2 beta-barrel domains, which are often involved in membrane interactions, and that the functionally important substitutions are clustered at one extremity of the domain. The combined findings suggest that the C-terminal region of alpha-toxin mediates interactions with membrane phospholipids in a calcium-dependent manner. Mutations to this domain may account for the natural lack of toxicity of the alpha-toxin homologue, phospholipase C of Clostridium bifermentans.

Dates and versions

pasteur-03136646 , version 1 (09-02-2021)

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Isabelle Guillouard, Pedro Alzari, Bernard Saliou, Stewart Cole. The carboxy‐terminal C 2 ‐like domain of the α‐toxin from Clostridium perfringens mediates calcium‐dependent membrane recognition. Molecular Microbiology, 2003, 26 (5), pp.867-876. ⟨10.1046/j.1365-2958.1997.6161993.x⟩. ⟨pasteur-03136646⟩

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