Three dimensional structure of the anthrax toxin translocon-lethal factor complex by cryo-electron microscopy

Area of Science:

• Structural biology
• Biophysics
• Microbiology

Background:

• Anthrax toxin requires protective antigen (PA) to translocate lethal factor (LF) into host cells.
• Understanding the PA translocon structure is crucial for developing therapeutics.

Purpose of the Study:

• To visualize the structure of the anthrax PA translocon complexed with LF(N) in a lipid bilayer.
• To elucidate the structural basis of toxin translocation.

Main Methods:

• Cryo-electron microscopy (cryo-EM) single-particle analysis.
• Three-dimensional reconstruction at 16 Å resolution.
• Nanodisc model lipid bilayer system.

Main Results:

• Visualized the PA translocon with LF(N) inserted into a nanodisc.
• Determined the structure of the complex, revealing a globular cap, stalk, and transmembrane channel.
• Observed distinct protrusions on the cap rim, influenced by LF(N).

Conclusions:

• The cryo-EM structure provides insights into the anthrax toxin translocation mechanism.
• The PA pore structure is consistent with its role in delivering LF into cells.
• Further structural studies are needed to fully resolve the translocon components.