Brooke J S, Cha J H
Department of Microbiology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, Texas 75235-9048, USA.
Biochem Biophys Res Commun. 2000 Aug 28;275(2):374-81. doi: 10.1006/bbrc.2000.3317.
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.
先前已确定白喉毒素（DT）与其受体结合所必需的主要氨基酸。W. H. 沈等人（《生物化学杂志》269, 29077 - 29084, 1994）以及J. H. 查等人（《分子微生物学》29(5), 1275 - 1284, 1998）的研究表明，DT单个氨基酸残基（516）赖氨酸的带正电性质对于与DT受体的结合至关重要，而DT受体带负电的（141）谷氨酸是毒素结合的最重要残基。在此，我们假设这两个带相反电荷的氨基酸残基之间发生关键相互作用。对毒素和受体在这些位置的残基进行了相互替换，这导致毒素与受体相互作用的部分重构。本研究提供了首个生物学数据，表征了这两个关键残基之间的特异性相互作用，以及DT其他带正电残基与DT受体（141）谷氨酸之间的额外相互作用。
