Low pH induces a hydrophobic domain in the tetanus toxin molecule

Abstract

Binding of the non‐ionic detergent [3H]Triton X‐100 by tetanus toxin, by its fragment C and by its a chain has been studied. At pH 4.00 or above, tetanus toxin does not bind Triton X‐100. At pH lower than 4.00, binding of detergent to the toxin occurs. At pH 3.00, a maximum of 100 mol bound/mol of protein is reached only when the detergent concentration exceeds its critical micelle concentration. No measurable amount of Triton X‐100 is bound by the toxin C fragment at pH 3.00. Most of the tetanus toxin α chain precipitates out in Triton X‐100 at pH 3.00. Leakage of K+ from single‐walled asolectin vesicles loaded with potassium was observed with tetanus toxin at pH lower than 4.00. When ganglioside GDlb was present on the asolectin vesicles, release of K+ was obtained with tetanus toxin between pH 4.00 to 5.00. We suggest that, as for diphtheria toxin, entry of tetanus toxin into an acidic compartment of target cells might be required for the expression of its biological activity.

Formation of ion channels in lipid bilayers by a peptide with the predicted transmembrane sequence of botulinum neurotoxin A

“…This property is compatible with the ionchannel activity observed when BoTxA, B, C, D, and E are reconstituted in lipid bilayers (Hoch et al, 1985;Donovan & Middlebrook, 1986;Blaustein et al, 1987). It has been proposed that such a channel is the conduit through which the LC gets access to the cytosol, where it acts (Boquet et al, 1976;Hoch et al, 1985;Donovan & Middlebrook, 1986;Blaustein et a]., 1987).…”

A Heterologous Reporter Defines the Role of the Tetanus Toxin Interchain Disulfide in Light-Chain Translocation

“…There are several approaches to measure LC translocation to the cytosol, including channel conductance using patch clamping, ion release from liposomes, and substrate cleavage in cultured cells (31,(37)(38)(39). To investigate LC translocation from intracellular vesicles into the cytosol of intact neuronal cells, ␤lac was engineered to the N terminus of the atoxic TeNT(RY).…”

On the role of polysialoglycosphingolipids as tetanus toxin receptors

“…The small effect of ionic strength indicates that hydrophobic interactions play an important role. The fact that tetanus toxin does not bind Triton X-100 at neutral pH, [52] and does not aggregate in solution, suggest that hydrophobic portions of the toxin are exposed upon interaction with the monolayer surface.…”