Divalent metal ion coordination by residue T118 of anthrax toxin receptor 2 is not essential for protective antigen binding

PLoS One. 2006 Dec 20;1(1):e99. doi: 10.1371/journal.pone.0000099.


The protective antigen (PA) subunit of anthrax toxin interacts with the integrin-like I domains of either of two cellular receptors, ANTXR1 or ANTXR2. These I domains contain a metal ion-dependent adhesion site (MIDAS) made up of five non-consecutive amino acid residues that coordinate a divalent metal ion that is important for PA-binding. The MIDAS residues of integrin I domains shift depending upon whether the domain exists in a closed (ligand-unbound) or open (ligand-bound) conformation. Of relevance to this study, the MIDAS threonine residue coordinates the metal ion only in the open I domain conformation. Previously it was shown that the MIDAS threonine is essential for PA interaction with ANTXR1, a result consistent with the requirement that the I domain of that receptor adopts an open conformation for PA-binding. Here we have tested the requirement for the MIDAS threonine of ANTXR2 for PA-binding. We show that the toxin can bind to a mutant receptor lacking the MIDAS threonine and that it can use that mutant receptor to intoxicate cultured cells. These findings suggest that an open-like configuration of the ANTXR2 MIDAS is not essential for the interaction with PA.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, Bacterial / chemistry
  • Antigens, Bacterial / metabolism*
  • Bacterial Toxins / chemistry
  • Bacterial Toxins / metabolism*
  • Binding Sites
  • CHO Cells
  • Cations, Divalent / metabolism
  • Cricetinae
  • Cricetulus
  • Humans
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Protein Structure, Tertiary
  • Receptors, Peptide
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Threonine / chemistry


  • ANTXR2 protein, human
  • Antigens, Bacterial
  • Bacterial Toxins
  • Cations, Divalent
  • Membrane Proteins
  • Receptors, Peptide
  • Recombinant Fusion Proteins
  • anthrax toxin
  • Threonine