ALPHA-HEMOLYSIN FROM STAPHYLOCOCCUS-AUREUS - AN ARCHETYPE OF BETA-BARREL, CHANNEL-FORMING TOXINS

alpha-Hemolysin, secreted from Staphylococcus aureus as a water-solubl e monomer of 33.2 kDa, assembles on cell membranes to form transmembra ne, heptameric channels. The structure of the detergent-solubilized he ptamer has been determined by X-ray crystallography to 1.9 Angstrom re solution. The heptamer has a mushroom-like shape and measures up to 10 0 Angstrom in diameter and 100 Angstrom in height. Spanning the length of the molecule and coincident with the molecular sevenfold axis is a water-filled channel that ranges in diameter from similar to 16 to si milar to 46 Angstrom. A 14 strand antiparallel beta-barrel, in which t wo strands are contributed by each subunit, defines the trans-membrane domain. On the exterior of the beta-barrel there is a hydrophobic bel t approximately 30 Angstrom in width that provides a surface complemen tary to the nonpolar portion of the lipid bilayer. The extensive proto mer-protomer interfaces are composed of both salt-links and hydrogen b onds, as well as hydrophobic interactions, and these contacts provide a molecular rationalization for the stability of the heptamer in SDS s olutions up to 65 degrees C. With the structure of the heptamer in han d, we can better understand the mechanisms by which the assembled prot ein interacts with the membrane and can postulate mechanisms of assemb ly. (C) 1998 Academic Press.