Molecular characterization of key diphtheria toxin:receptor interactions.
The major amino acids necessary for diphtheria toxin (DT) binding to its receptor have been identified previously. Studies by W. H. Shen et al. (J. Biol. Chem. 269, 29077-29084, 1994) and by J. H. Cha et al. (Mol. Microbiol. 29 (5), 1275-1284, 1998) suggested that the positively charged nature of the single amino acid residue, (516)Lys of DT, is crucial for binding to the DT receptor, whereas the negatively charged (141)Glu of the DT receptor is the most important residue for toxin binding. Here, we hypothesize that key interactions occur between these two oppositely charged amino acid residues. Reciprocal substitution of the residues at these positions between the toxin and the receptor was performed, which resulted in a partial reconstitution of the toxin:receptor interaction. This study provides the first biological data that characterizes the specific interaction of these two key residues with each other and also the additional interactions between other positively charged residues of DT and (141)Glu of the DT receptor.
Brooke
J S
JS
Department of Microbiology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, Texas 75235-9048, USA.
Cha
J H
JH
D000818:Animals; D002460:Cell Line; D004167:Diphtheria Toxin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D008239:Lysine / Q000737:chemistry / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*
D004167:Diphtheria Toxin; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface; D008239:Lysine