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Large-scale structural changes accompany binding of lethal factor to anthrax protective antigen: a cryo-electron
Gang Ren1, Joel Quispe, Stephen H Leppla
1Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Structure (London, England : 1993)
|November 9, 2004
Summary
Anthrax toxin's lethal factor (LF) interacts with protective antigen (PA63h), causing structural changes. This reorganization likely facilitates LF translocation into host cells, a key step in anthrax toxicity.
Area of Science:
- Microbiology
- Structural Biology
- Biochemistry
Background:
- Anthrax toxin (AT) comprises lethal factor (LF), edema factor (EF), and protective antigen (PA).
- Toxicity involves ligand (LF/EF) binding to a PA63 heptamer (PA63h) and translocation into the cytosol.
- The mechanism of translocation remains largely unknown.
Purpose of the Study:
- To visualize the structural interaction between PA63h and LF.
- To elucidate the structural basis for LF translocation across the cell membrane.
Main Methods:
- Cryo-electron microscopy (cryo-EM) was used to analyze the PA63h.LF complex.
- Specimens were suspended in vitrified buffer for imaging.
Main Results:
- Direct visualization of the PA63h.LF complex revealed LF's interaction with four PA63 monomers.
- This interaction caused partial unraveling of the PA63h heptamer, widening its central lumen.
- LF was localized to the non-membrane-interacting face of the oligomer.
Conclusions:
- Structural reorganization of PA63h upon LF binding facilitates translocation.
- The widened lumen likely accommodates the passage of the 90 kDa LF molecule.
- Cryo-EM provides insights into anthrax toxin translocation mechanisms.