STRUCTURE OF STAPHYLOCOCCAL ALPHA-HEMOLYSIN, A HEPTAMERIC TRANSMEMBRANE PORE

The structure of the Staphylococcus aureus alpha-hemolysin pore has be en determined to 1.9 Angstrom resolution. Contained within the mushroo m-shaped homo-oligomeric heptamer is a solvent-filled channel, 100 Ang strom 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 w hich each protomer contributes two beta strands, each 65 Angstrom long . The interior of the beta barrel is primarily hydrophilic, and the ex terior has a hydrophobic belt 28 Angstrom wide. The structure proves t he heptameric subunit stoichiometry of the alpha-hemolysin oligomer, s hows that a glycine-rich and solvent-exposed region of a water-soluble protein can self-assemble to form a transmembrane pore of defined str ucture, and provides insight into the principles of membrane interacti on and transport activity of beta barrel pore-forming toxins.