Mode of action of β-barrel pore-forming toxins of the staphylococcal α-hemolysin family

Staphylococcal alpha -hemolysin is the prototype of a family of bacterial exotoxins with membrane-damaging function, which share sequence and structure homology. These toxins are secreted in a soluble form which finally converts into a transmembrane pore by assembling an oligomeric beta -barrel, with hydrophobic residues facing the lipids and hydrophilic residues facing the lumen of the channel. Besides alpha -hemolysin the family includes other single chain toxins forming homo-oligomers, e.g. betatoxin of Clostridium perfringens, hemolysin II and cytotoxin K of Bacillus cereus, but also the staphylococcal bi-component toxins, like gamma -hemolysins and leucocidins, which are only active as the combination of two similar proteins which form heterooligomers. The molecular basis of membrane insertion has become clearer after the determination of the crystal structure of both the oligomeric pore and the soluble monomer. Studies on this family of beta -barrel pore-forming toxins are important for many aspects: (i) they are involved in serious pathologies of humans and farmed animals, (ii) they are a good model system to investigate protein-membrane interaction and (iii) they are the basic elements for the construction of nanopores with biotechnological applications in various fields. (C) 2001 Elsevier Science Ltd. All rights reserved.