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, 516Lys of DT, is crucial for binding to the DT receptor, whereas the negatively charged 141Glu 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 141Glu of the DT receptor. (C) 2000 Academic Press.
|Number of pages||8|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 2000 Aug 28|
Bibliographical noteFunding Information:
The authors thank Dr. R. J. Collier for the generous gift of mutant DT K516E. We also thank Dr. Yong-Hwan Lee for assistance with the diagram of the crystal structure. The advice and editorial assistance of Dr. Leon Eidels is greatly appreciated. This work was supported by U.S. Public Health Service Grant AI-16805.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology