An anthrax bacterium secretes three nontoxic proteins that assemble into a toxic complex on the surface of the host cell to set off a chain of events leading to cell toxicity and death. Protective antigen (PA) is one of these proteins, and after binding to the cell, seven copies of it assemble into a specific complex that is capable of forming a pore in a cellular membrane. The pore permits the other two proteins, lethal factor (LF) and edema factor (EF), to enter the cell interior, where the factors interfere with metabolic processes, leading to death of the infected individual.
Details surrounding this process are continuing to be uncovered in Collier's lab. "Until now, we have not known whether the PA pore serves simply as a passive conduit, or alternatively, plays an active role in shepherding the unfolded LF and EF molecules through," he said. The findings show that it is the latter?the pore takes an active role in protein translocation.
The scientists demonstrated this role by investigating the channel's chemical make-up. Using a procedure known as cysteine-scanning mutagenesis, they identified the hydrophobic, or "greasy," amino acid phenylalanine in protective antigen's pore-forming domain. Seven of these amino acids project into the lumen of the pore and form a collection of greasy residues, nicknamed "the phi-clamp" by the sc
Contact: Leah Gourley or John Lacey
Harvard Medical School