Abstract
THE seven botulinum neurotoxin (NT) serotypes produced by strains of Clostridium botulinum inhibit neurotransmitter release from synaptic vesicles. Neurotoxin is synthesized as a roughly 150K single-chain protein. Proteolysis produces two fragments, the 50K L-chain and 100K H-chain, that remain linked by a disulphide bond. Intoxication involves membrane attachment by the C-terminal half of the H-chain, endocytotic/lysosomal internalization, vesicle channel formation mediated by the 50K N-terminal half of the H-chain at low pH, and finally blockade of synaptic vesicle fusion after the L-chain reaches the cytosol1–4. We report here the visualization of the neurotoxin–membrane complex by electron cryomicroscopy and image processing. Three-dimensional reconstructions show the neurotoxin bound to the exterior of ganglioside/PC lipid vesicles and show channels entirely perforating the vesicle wall. Each channel appears to arise from the interaction of four neurotoxin molecules.
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References
Simpson, L. L. (ed.) Botulinum Neurotoxin and Tetanus Toxin (Academic, San Diego, 1989).
DasGupta, B. R. J. Physiol., Paris 84, 220–228 (1990).
Dolly, J. O. et al. J. Physiol., Paris 84, 237–246 (1990).
Simpson, L. L. A. Rev. Pharmacol. Toxicol. 26, 427–453 (1986).
Robinson, J. P., Schmid, M. F., Morgan, D. G. & Chiu, W. J. molec. Biol. 200, 367–375 (1988).
Kornberg, R. D. & Darst, S. A. Curr. Opin. Struct. Biol. 1, 632–646 (1991).
Chang, C. F. et al. J. Ultrastruct. molec. Struct. Res. 100, 166–172 (1988).
Schmid, M. F., DasGupta, B. R. & Robinson, J. P. Proc. XII Int. Congr. Electron Microscopy, Seattle, 1990, 496–497 (San Francisco, 1990).
Hoch, D. H. & Finkelstein, A. Ann. NY. Acad. Sci. 456, 33–35 (1985).
Donovan, J. J. & Middlebrook, J. L. Biochemistry 25, 2872–2876 (1986).
Montal, M. S. et al. FEBS Lett. 313, 12–18 (1992).
Binz, T. et al. J. biol. Chem. 265, 9153–9158 (1990).
Hoch, D. H. et al. Proc. natn. Acad. Sci. U.S.A. 82, 1692–1696 (1985).
Schmid, M. F. et al. J. molec. Biol. 221, 711–725 (1991).
Grant, R. A. et al. Biophys. J. 49, 251–258 (1986).
DeRosier, D. J. & Moore, P. B. J. molec. Biol. 52, 355–369 (1970).
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Schmid, M., Robinson, J. & DasGupta, B. Direct visualization of botulinum neurotoxin-induced channels in phospholipid vesicles. Nature 364, 827–830 (1993). https://doi.org/10.1038/364827a0
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DOI: https://doi.org/10.1038/364827a0
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