The structure of Staphylococcus aureus alpha-toxin-induced ionic channel

Area of Science:

• Biophysics
• Membrane Biology
• Toxicology

Background:

• Alpha-staphylotoxin (ST) forms pores in cell membranes, leading to osmotic lysis.
• Polyethylene glycols (PEG) are polymers with potential protective effects on cell membranes.

Purpose of the Study:

• To investigate the protective effects of PEG on human erythrocytes against ST-induced lysis.
• To characterize the biophysical properties of ST-induced ion channels in lipid bilayers.
• To elucidate the structure and membrane interaction of the ST-channel.

Main Methods:

• Erythrocyte protection assays using PEG of varying molecular weights.
• Electrophysiological measurements (conductivity, current-voltage characteristics) in bilayer lipid membranes (BLM).
• Comparative studies using phosphatidylcholine (PC) and phosphatidylserine (PS) lipid bilayers.

Main Results:

• PEG (MW ≤ 3000) effectively protected erythrocytes from ST-induced osmotic lysis.
• PEG did not alter the conductivity of ST-induced channels in BLM.
• Changing bilayer composition to negatively charged PS induced asymmetry in current-voltage characteristics, indicating asymmetrical ST-channel pore positioning.
• The ST-channel was characterized as an interprotein pore (2.5-3 nm diameter, ~10 nm length) formed by six alpha-toxin molecules.

Conclusions:

• PEG offers protection against ST-induced erythrocyte lysis.
• The ST-channel exhibits an asymmetrical structure within the lipid bilayer, with one end interacting with lipid heads and the other protruding into the aqueous solution.
• The findings provide insights into the mechanism of ST-induced membrane damage and potential protective strategies.