Structure of staphylococcal alpha-hemolysin, a heptameric transmembrane pore

Area of Science:

• Structural biology
• Microbiology
• Biochemistry

Background:

• Staphylococcus aureus alpha-hemolysin is a key virulence factor.
• Pore-forming toxins play a significant role in microbial pathogenesis.
• Understanding toxin structure is crucial for developing countermeasures.

Purpose of the Study:

• To determine the high-resolution structure of the Staphylococcus aureus alpha-hemolysin pore.
• To elucidate the mechanism of self-assembly and membrane insertion.
• To gain insights into the structure-function relationship of beta-barrel pore-forming toxins.

Main Methods:

• X-ray crystallography at 1.9 A resolution.
• Analysis of oligomeric structure and channel architecture.
• Characterization of protein-membrane interactions.

Main Results:

• The homo-oligomeric heptameric structure of the alpha-hemolysin pore was resolved.
• A central, solvent-filled channel (100 A long, 14-46 A diameter) was identified along the sevenfold axis.
• The lytic domain consists of a 14-strand antiparallel beta-barrel with hydrophilic interior and hydrophobic exterior belt.

Conclusions:

• The heptameric stoichiometry of alpha-hemolysin was confirmed.
• A water-soluble protein region can self-assemble into a functional transmembrane pore.
• The structure provides a basis for understanding membrane interaction and transport by beta-barrel toxins.