STAPHYLOCOCCAL ALPHA-HEMOLYSIN CAN FORM HEXAMERS IN PHOSPHOLIPID-BILAYERS

Atomic force microscopy (AFM) was used to study the structure of the s taphylococcal alpha-hemolysin (alpha HL) oligomer formed in supported phospholipid bilayers. In contrast to the recent X-ray crystallographi c demonstration of a heptameric stoichiometry for the oligomer formed in deoxycholate (DOC) micelles, the high-resolution unprocessed AFM im ages unequivocally revealed a hexamer in these phospholipid bilayers. Independent support of this hexameric stoichiometry was obtained from the measurements of the lattice constant in the AFM images and from ge l electrophoresis. Therefore, alpha HL can form two different, energet ically stable oligomers, which differ in at least stoichiometry but pe rhaps subunit structure as well. Furthermore, stable, incomplete oligo mers were observed in the AFM images, which may be of relevance to the mechanism by which alpha HL damages the cell. (C) 1998 Academic Press Limited.