Structure of Staphylococcal α-Hemolysin, a Heptameric Transmembrane Pore

TLDR

The α‑hemolysin heptamer forms a mushroom‑shaped pore with a 100‑Å long, 14–46‑Å diameter solvent‑filled channel and a 14‑strand antiparallel β‑barrel whose interior is hydrophilic and exterior hydrophobic. The 1.9‑Å crystal structure confirms the heptameric stoichiometry, demonstrates that a glycine‑rich, solvent‑exposed region of a soluble protein can self‑assemble into a defined transmembrane β‑barrel pore, and offers insights into membrane interaction and transport of β‑barrel toxins.

Abstract

The structure of the Staphylococcus aureus α-hemolysin pore has been determined to 1.9 Å resolution. Contained within the mushroom-shaped homo-oligomeric heptamer is a solvent-filled channel, 100 Å in length, that runs along the sevenfold axis and ranges from 14 Å to 46 Å in diameter. The lytic, transmembrane domain comprises the lower half of a 14-strand antiparallel β barrel, to which each protomer contributes two β strands, each 65 Å long. The interior of the β barrel is primarily hydrophilic, and the exterior has a hydrophobic belt 28 Å wide. The structure proves the heptameric subunit stoichiometry of the α-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 β barrel pore-forming toxins.