title: Disulfide bond reduction corresponds to dimerization and hydrophobi-city changes of Clostridium botulinum type A neurotoxin.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Preventive Medicine, National Defense Center, Taipei, Taiwan 115, China.
authors.forename: Jiunn-jye
authors.initials: JJ
authors.lastname: Wey
authors.forename: Shiao-shek
authors.initials: SS
authors.lastname: Tang
authors.forename: Tzong-yuan
authors.initials: TY
authors.lastname: Wu
mesh_terms: D019274:Botulinum Toxins, Type A / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D003014:Clostridium botulinum / Q000737:chemistry; D018360:Crystallography, X-Ray; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007473:Ion Channels / Q000096:biosynthesis*; D020836:Protein Structure, Quaternary
chemical_list: D004220:Disulfides; D007473:Ion Channels; D019274:Botulinum Toxins, Type A