Research from D.S. Anderson and colleagues has provided new data on anthrax
December 8th, 2008
2008 DEC 8 -- According to a study from the United States, "The channel-forming component of anthrax toxin, (PA(63))(7), is a heptameric water-soluble protein at neutral pH, but under acidic conditions it spontaneously inserts into lipid bilayers to form a 14-stranded beta-barrel ion-conducting channel. This channel plays a vital role in anthrax pathogenesis because it serves as a conduit for the membrane translocation of the two enzymatic components of anthrax toxin, lethal factor and edema factor."
"Anthrax channels open and close in response to changes in transmembrane voltage, a property shared by several other pore-forming toxins. We have discovered an unexpected phenomenon in cysteine-substituted channels that provides a window into this gating process: their normal voltage-dependent gating can be abolished by reaction with methanethiosulfonate (MTS) reagents or exposure to oxidizing conditions. Remarkably, this perturbation is seen with cysteines substituted at sites all along the similar to 100 angstrom length of the channel's beta-barrel. In contrast, reaction with N-ethylmaleimide, a thiol-reactive compound that does not form a mixed disulfide, does not affect gating at any of the sites tested," wrote D.S. Anderson and colleagues.
The researchers concluded: "These findings, coupled with our biochemical detection of dimers, have led us to conclude that MTS reagents are catalyzing the formation of intersubunit disulfide bonds that lock channels in a conducting state, and that voltage gating requires a conformational change that involves the entire beta-barrel."
Anderson and colleagues published the results of their research in the Journal of General Physiology (Preventing voltage-dependent gating of anthrax toxin channels using engineered disulfides. Journal of General Physiology, 2008;132(3):351-360).
For additional information, contact R.O. Blaustein, Tufts Med Center, Molecular Cardiology Research Institute, Boston, MA 02111, USA.
The publisher of the Journal of General Physiology can be contacted at: Rockefeller University Press, 1114 First Avenue, 4TH FL, New York, NY 10021, USA.
