Open AccessDisulfide bond reduction corresponds to dimerization and hydrophobicity changes of Clostridium botulinum type A neurotoxin
Author(s) -
WEY Jiunnjye,
TANG Shiaoshek,
WU Tzongyuan
Publication year - 2006
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2006.00372.x
Subject(s) - chemistry , clostridium botulinum , botulism , protein quaternary structure , neurotoxin , disulfide bond , botulinum neurotoxin , biophysics , stereochemistry , crystallography , toxin , biochemistry , protein subunit , microbiology and biotechnology , gene , biology
Aim: To determine the structure factors that mediate the intoxication process of botulinum neurotoxin type A (BoNT/A). Methods: Triton X‐114 phase separation experiments and 1‐anilino‐8‐naphthalene sulfonate binding assay were used to study the structural factor that corresponds to the hydrophobicity change of BoNT/A. In addition, sucrose density gradient centrifugation and a chemical crosslinking study were employed to determine the quaternary structure of BoNT/ A. Results: Our results demonstrated that in other than acidic conditions, the disulfide reduction is the structural factor that corresponds to the hydrophobicity change of BoNT/A. The quaternary structure of BoNT/A exists as a dimmer in acidic solution (pH 4.5), although the monomeric structure of BoNT/A was reported based on X‐ray crystallography. Conclusion: Disulfide bond reduction is critical for BoNT/A's channel formation and ability to cross endosome membranes. This result implies that compounds that block this disulfide bond reduction may serve as potential therapeutic agents for botulism.