E. coli α-hemolysin: A membrane-active protein toxin

Abstract

α-Hemolysin is synthesized as a 1024-amino acid polypeptide, then intracellularly activated by specific fatty acylation. A second activation step takes place in the extracellular medium through binding of Ca2+ ions. Even in the absence of tatty acids and Ca2+ HlyA is an amphipathic protein, with a tendency to self-aggregation. However, Ca2+-binding appears to expose hydrophobic patches on the protein surface, facilitating both self-aggregation and irreversible insertion into membranes. The protein may somehow hind membranes in the absence of divalent cations, hut only when Ca2+ (or Sr2+ , or Ba2+) is bound to the toxin in aqueous suspensions, i.e., prior to its interaction with bilayers, can α-hemolysin bind irreversibly model or cell membranes in such a way that the integrity of the membrane harrier is lost, and cell or vesicle leakage ensues. Leakage is not due to the formation of proteinaceous pores, but rather to the transient disruption of the bilayer, due to the protein insertion into the outer membrane monolayer, and subsequent perturbations in the bilayer lateral tension. Protein or glycoprotcin receptors for α-hemolysin may exist on the cell surface, but the toxin is also active on pure lipid bilayers.