The channel-forming toxin aerolysin

Abstract

Aeromonas sp. secrete a precursor of the cytolytic protein aerolysin into the culture medium, where it is activated by proteolytic removal of a C-terminal fragment. Activation can be achieved by a variety of mammalian proteases as well as by proteases released by the bacteria itself. Activated toxin binds with high affinity to the transmembrane protein glycophorin on the surface of eucaryotic cells. Binding is followed by oligomerization and the formation of transmembrane channels, leading to cell death. Using chemical modification and site-directed mutagenesis, we have identified regions of the molecule which are important in transfer across the outer membrane of the bacteria, and in proteolytic activation, binding, and oligomerization. A preliminary electron density map of proaerolysin crystals indicates that the protein is organized into three domains. Analysis of two-dimensional crystals of aerolysin suggests that the oligomeric form of the protein is heptameric.