Molecular Basis of Low pH-Dependent Membrane Translocation of Botulinum and Tetanus Neurotoxins

Abstract

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.