Synchronized chaperone function of botulinum neurotoxin domains mediates light chain translocation into neurons.

摘要: Clostridium botulinum neurotoxin (BoNT) is a multidomain protein in which the individual modules work synchronized cooperative action order to enter into neurons and inhibit synaptic transmission. The di-chain made up of ~50 kD light chain ~100 heavy chain. HC can be further subdivided N-terminal translocation domain (HN) C-terminal Receptor Binding Domain (HC). BoNT entry requires toxin utilize host cell’s endocytosis pathway where it exploits acidic environment endosome. Within endosome triggers HN change conformation from soluble membrane inserted protein-conducting channel precise timing with LC refolding. must partially unfold competent translocated by an N C terminal direction. Upon completion translocation, released allowed interact its substrate SNARE protein. This article discusses functions each module as well mechanisms serves chaperone for others, working concert achieve productive intoxication.