Translocation of botulinum neurotoxin light chain protease by the heavy chain protein-conducting channel.

ABSTRACT: Clostridial botulinum neurotoxins (BoNTs) inhibit synaptic exocytosis; intoxication requires the di-chain protein to undergo conformational changes in response to pH and redox gradients across the endosomal membrane with consequent formation of a protein-conducting channel by the heavy chain (HC) that translocates the light chain (LC) protease into the cytosol, colocalizing it with the substrate SNARE proteins. We investigate the dynamics of protein translocation across membranes using a sensitive single-molecule assay to track translocation events with millisecond resolution on lipid bilayers and on membrane patches of Neuro 2A cells. Translocation of BoNT/A LC by the HC is observed in real time as changes of channel conductance: the channel is occluded by the light chain during transit,

SUBMITTER: Montal M 

PROVIDER: S-EPMC2782371 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature