Structure of staphylococcal alpha-hemolysin, a heptameric transmembrane pore

The structure of the Staphylococcus aureus alpha-hemolysin pore has been determined to 1.9 Angstrom resolution. Contained within the mushroom-shaped homo-oligomeric heptamer is a solvent-filled channel, 100 Angstrom in length, that runs along the sevenfold axis and ranges from 14 Angstrom to 46 Angstrom in diameter. The lytic, transmembrane domain comprises the lower half of a 14-strand antiparallel beta barrel, to which each protomer contributes two beta strands, each 65 Angstrom long. The interior of the beta barrel is primarily hydrophilic, and the exterior has a hydrophobic belt 28 Angstrom wide. The structure proves the heptameric subunit stoichiometry of the alpha-hemolysin oligomer, shows that a glycine-rich and solvent-exposed region of a water-soluble protein can self-assemble to form a transmembrane pore of defined structure, and provides insight into the principles of membrane interaction and transport activity of beta barrel pore-forming toxins.