Tetanus toxin is labeled with photoactivatable phospholipids at low pH

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• The mechanism of tetanus toxin cell penetration remains unclear.
• A proposed mechanism involves penetration from a low-pH vesicular compartment into the lipid bilayer.

Purpose of the Study:

• To investigate the interaction of tetanus toxin with model membranes.
• To elucidate the role of pH and lipid composition in toxin-membrane interactions.

Main Methods:

• Photoinduced cross-linking of tetanus toxin with liposomal model membranes.
• Use of light-sensitive phosphatidylcholine analogues to generate nitrene or carbene.
• pH-dependent labeling and characterization of toxin hydrophobicity.

Main Results:

• Tetanus toxin labeling occurred only at pHs below 5.5.
• Low pH induces hydrophobicity in the toxin's light chain and a 45-kDa heavy chain fragment.
• Negatively charged lipids facilitate toxin interaction with phospholipid hydrocarbon chains.

Conclusions:

• Tetanus toxin exhibits pH-dependent membrane interaction, with specific domains becoming hydrophobic at low pH.
• The findings suggest a mechanism for tetanus toxin entry into nerve cells involving lipid bilayer interaction.
• Negatively charged lipids play a role in promoting toxin association with the membrane.