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.