Transformation of a non-enzymatic toxin into a toxoid by genetic engineering |
| |
Authors: | Fromen-Romano C; Maillere B; Drevet P; Lajeunesse E; Ducancel F; Boulain JC; Menez A |
| |
Affiliation: | Departement d'Ingenierie et d'Etudes des Proteines, DSV, CEA Saclay, Gif-sur-Yvette, France. |
| |
Abstract: | Curaremimetic toxins are typical non-enzymatic toxins that bind to their
target the nicotinic acetylcholine receptor (AChR)] through multiple
residues. Nevertheless, we show that the concomitant substitutions of only
three of the ten functionally important residues of such a toxin sufficed
to cause an affinity decrease of the toxin for AChR that is higher than
four orders of magnitude. Despite these triple mutations, the overall
conformation of the mutated protein remains similar to that of a related
recombinant toxin, as judged from both circular dichroism analysis and
investigation of antigenicity, using monoclonal and polyclonal antibodies.
Furthermore, we show that the detoxified toxin is capable of eliciting
antibodies that neutralize the binding of a wild-type toxin to AChR.
Therefore, transformation of a non-enzymatic toxin into a toxoid can be
achieved, like in the case of enzymatic toxins, by introducing a small
number of mutations at positions identified to be critical for expression
of toxicity.
|
| |
Keywords: | |
本文献已被 Oxford 等数据库收录! |
|