The crystal structure of diphtheria toxin

Abstract

The crystal structure of the diphtheria toxin dimer at 2.5 Å resolution reveals a Y-shaped molecule of three domains. The catalytic domain, called fragment A, is of the α + β type. Fragment B actually consists of two domains. The transmembrane domain consists of nine α-helices, two pairs of which are unusually apolar and may participate in pH-triggered membrane insertion and translocation. The receptor-binding domain is a flattened β-barrel with a jelly-roll-like topology. Three distinct functions of the toxin, each carried out by a separate structural domain, can be useful in designing chimaeric proteins, such as immunotoxins, in which the receptor-binding domain is substituted with antibodies to target other cell types.

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Choe, S., Bennett, M., Fujii, G. et al. The crystal structure of diphtheria toxin. Nature 357, 216–222 (1992). https://doi.org/10.1038/357216a0

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