A model of anthrax toxin lethal factor bound to protective antigen

D. Borden Lacy, Henry C. Lin, Roman A. Melnyk, Ora Schueler-Furman, Laura Reither, Kristina Cunningham, David Baker, John R. Collier*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


Anthrax toxin is made up of three proteins: the edema factor (EF), lethal factor (LF) enzymes, and the multifunctional protective antigen (PA). Proteolytically activated PA heptamerizes, binds the EF/LF enzymes, and forms a pore that allows for EF/LF passage into host cells. Using directed mutagenesis, we identified three LF-PA contact points defined by a specific disulfide crosslink and two pairs of complementary charge-reversal mutations. These contact points were consistent with the lowest energy LF-PA complex found by using Rosetta protein-protein docking. These results illustrate how biochemical and computational methods can be combined to produce reliable models of large complexes. The model shows that EF and LF bind through a highly electrostatic interface, with their flexible N-terminal region positioned at the entrance of the heptameric PA pore and thus poised to initiate translocation in an N- to C-terminal direction.

Original languageAmerican English
Pages (from-to)16409-16414
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number45
StatePublished - 8 Nov 2005
Externally publishedYes


  • Computation
  • Docking
  • Electrostatic


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