Anthrax toxin complexes: heptameric protective antigen can bind lethal factor and edema factor simultaneously

Biochem Biophys Res Commun. 2004 Sep 10;322(1):258-62. doi: 10.1016/j.bbrc.2004.07.105.

Abstract

The 83 kDa protective antigen (PA(83)) component of anthrax toxin, after proteolytic activation, self-associates to form ring-shaped heptamers ([PA(63)](7)) that bind and aid delivery of the Edema Factor (EF) and Lethal Factor (LF) components to the cytosol. Here we show using fluorescence (Förster) resonance energy transfer that a molecule of [PA(63)](7) can bind EF and LF simultaneously. We labeled EF and LF with an appropriate donor/acceptor pair and found quenching of the donor and an increase in sensitized emission of the acceptor when, and only when, a mixture of the labeled proteins was combined with [PA(63)](7). Addition of unlabeled PA(63)-binding domain of LF to the mixture competitively displaced labeled EF and LF, causing a loss of energy transfer. In view of the known maximum occupancy of 3 ligand molecules per [PA(63)](7), these findings indicate that PA, EF, and LF can form mixtures of liganded toxin complexes containing both EF and LF.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, Bacterial / chemistry*
  • Bacterial Toxins / chemistry*
  • Binding Sites
  • Complex Mixtures / chemistry*
  • Fluorescence Resonance Energy Transfer
  • Macromolecular Substances
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Tertiary
  • Protein Subunits / chemistry

Substances

  • Antigens, Bacterial
  • Bacterial Toxins
  • Complex Mixtures
  • Macromolecular Substances
  • Protein Subunits
  • anthrax toxin