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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References
Greenfield, L. et al. Proc. natn. Acad. Sci. U.S.A. 80, 6853–6857 (1983).
Moskaug, J. O., Sletten, K., Sandvig, K. & Olsnes, S. J. biol. Chem. 264, 15709–15713 (1989).
Collier, R. J. & Kandel, J. J. biol. Chem. 246, 1496–1503 (1971).
Sandvig, K. & Olsnes, S. J. biol. Chem. 256, 9068–9076 (1981).
Yamaizumi, M., Mekada, E., Uchida, T. & Okada, Y. Cell 15, 245–250 (1978).
Colombatti, M., Dell'Arciprete, L., Rappuoli, R. & Tridente, G. Meth. Enzym. 178, 404–422 (1989).
Williams, D. P. et al. Prot. Engng 1, 493–498 (1987).
Chaudhary, V. K., Gallo, M. G., FitzGerald, D. J. & Pastan, I. Proc. natn. Acad. Sci. U.S.A. 87, 9491–9494 (1990).
Greenfield, L., Johnson, V. G. & Youle, R. J. Science 238, 536–539 (1987).
Papini, E. et al. Eur. J. Biochem. 169, 637–644 (1987).
Moskaug, J. O., Stenmark, H. & Olsnes, S. J. biol. Chem. 266, 2652–2659 (1991).
Blewitt, M. G., Chung, L. A. & London, E. Biochemistry 24, 5458–5464 (1985).
Kagan, B. L., Finkelstein, A. & Colombini, M. Proc. natn. Acad. Sci. U.S.A. 78, 4950–4954 (1981).
Donovan, J. J., Simon, M. I., Draper, R. K. & Montal, M. Proc. natn. Acad. Sci. U.S.A. 78, 172–176 (1981).
Collier, R. J., Westbrook, E. M., McKay, D. B. & Eisenberg, D. J. biol. Chem. 257, 5283–5285 (1982).
Carroll, S. F., Barbieri, J. T. & Collier, R. J. Biochemistry 25, 2425–2430 (1986).
Fujii, G., Choe, S., Bennett, M. J. & Eisenberg, D. J. molec. Biol. 222, 861–864 (1991).
Wang, B.-C. Meth. Enzym. 115, 90–112 (1985).
Brünger, A. T. Acta crystallogr. A47, 195–204 (1991).
Rossmann, M. G. & Blow, D. M. Acta crystallogr. 15, 24–31 (1962)
Zhang, K. Y. J. & Main, P. Acta crystallogr. A46, 377–381 (1991).
Lüthy, R., Bowie, J. U. & Eisenberg, D. Nature 356, 83–85 (1992).
Jones, T. A., Zou, J.-Y., Cowan, S. W. & Kjeldgaard, M. Acta crystallogr. A47, 110–119 (1991).
Brünger, A. T. Nature 355, 472–475 (1992).
Allured, V. S., Collier, R. J., Carroll, S. F. & McKay, D. B. Proc. natn. Acad. Sci. U.S.A. 83, 1320–1324 (1986).
Carroll, S. F. & Collier, R. J. Molec. Microbiol. 2, 293–296 (1988).
Brandhuber, B. J., Allured, V. S., Falbel, T. G. & McKay, D. B. Proteins 3, 146–154 (1988).
Sixma, T. K. et al. Nature 351, 371–377 (1991).
Parker, M. W., Pattus, F., Tucker, A. D. & Tsernoglou, D. Nature 337, 93–96 (1989).
Richardson, J. Adv. Prot. Chem. 34, 167–339 (1981).
Li, J. D., Carroll, J. & Ellar, D. J. Nature 353, 815–821 (1991).
Carroll, S. F. & Collier, R. J. Proc. natn. Acad. Sci. U.S.A. 81, 3307–3311 (1984).
Papini, E., Schiavo, G., Sandona, D., Rappuoli, R. & Montecucco, C. J. biol. Chem. 264, 12385–12388 (1989).
Papini, E. et al. J. biol. Chem. 266, 2494–2498 (1991).
Giannini, G., Rappuoli, R. & Ratti, G. Nucleic Acids Res. 12, 4063–4069 (1984).
Collins, C. M. & Collier, R. J. Biochim. biophys. Acta 828, 138–143 (1985).
Zhao, J.-M. & London, E. Biochemistry 27, 3398–3403 (1988).
Proia, R. L., Wray, S. K., Hart, D. A. & Eidels, L. J. biol. Chem. 255, 12025–12033 (1980).
Lory, S. & Collier, R. J. Proc. natn. Acad. Sci. U.S.A. 77, 267–271 (1980).
Rees, D. C., DeAntonio, L. & Eisenberg, D. Science 245, 510–513 (1989).
McLaughlin, S. Curr. Top. Memb. Trans. 9, 71–144 (1977).
Weissman, L. thesis, Univ. California (1979).
Terwilliger, T. C. Kim, S.-H. & Eisenberg, D. Acta crystallogr. A43, 1–5 (1987).
Jones, A. T. Meth. Enzym. 115, 157–171 (1985).
Ponder, J. W. & Richards, F. M. J. molec. Biol. 193, 775–791 (1987).
Brünger, A. T. & Krukowski, A. Acta crystallogr. A46, 585–593 (1990).
Marquart, M., Deisenhofer, J., Huber, R. & Palm, W. J. molec. Biol. 141, 369–391 (1980).
Eck, M. J. & Sprang, S. R. J. biol. Chem. 264, 17595–17605 (1989).
Jones, E. Y., Stuart, D. I. & Walker, N. P. C. Nature 338, 225–228 (1989).
Kiyokawa, T., Williams, D. P., Snider, C. E., Strom, T. B. & Murphy, J. R. Prot. Engng 4, 463–468 (1991).
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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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DOI: https://doi.org/10.1038/357216a0