Molecular Basis of Low pH-Dependent Membrane Translocation of Botulinum and Tetanus Neurotoxins
Botulinum and tetanus neurotoxins, structurally related proteins (150 kDa), attack the nervous system very rapidly, once inside the body; the toxins are quite soluble at pH 7 and are readily transported throughout the body. However, these proteins are known to form membranespanning channels at one point in the pathway of their toxic activity.1 A question is raised as to how a water soluble protein can integrate itself in a non-polar membrane bilayer. The protein must undergo some structural change, allowing it to assume enough hydrophobic or amphiphilic character to interact adequately with the membrane. Furthermore, this channel-forming activity is associated with the pH 4 environment of toxin-containing endosomes. The condition of pH 4 seems to be the incident in conferring this hydrophobic character upon the toxins.
KeywordsBotulinum Toxin Residue Number Tetanus Toxin Hydrophobicity Scale Hydrophobic Moment
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- 3.Eisenberg D, Wilcox W, Eshita S. Hydrophobic moments as tool for the analysis of protein sequences and structures. In: L’Italian JJ, ed. Protein Structure and Function. New York: Plenum Press, 1987: 425–436.Google Scholar
- 4.Singh BR, Be X. Use of sequence hydrophobic moment to analyze membrane interacting domains of botulinum, tetanus and other toxins. In: Angeletti RH, ed. Techniques. Protein Chem. Orlando, FL: Academic Press, 1992: 373–383.Google Scholar
- 8.Eisel U, Jarausch W, Goretzki K, Henschen A, Engels J, Weller U, et al. Tetanus toxin: primary structure, expression in E. coli, and homology with botulinum toxins. EMBO J 1986; 5: 2495–2502.Google Scholar