Translocation of BoNT Light chain Authored: Krupa, S, Gopinathrao, G, 2006-06-15 10:36:11 Edited: Gopinathrao, G, 2006-06-15 22:12:29 Pubmed12417130 Pubmed12459720 Pubmed13678859 Pubmed7527117 Pubmed8206166 Reactome Database ID Release 43181363 Reactome, http://www.reactome.org ReactomeREACT_11085 Reviewed: Ichtchenko, K, 2007-08-03 18:17:25 Translocation of the BoNT Light chain (LC) from an endocytic vesicle into the cytosol is essential for neurotoxicity. It has been proposed that acidic pH within the endosome triggers a conformational change in the Heavy chain (HC) N-terminal domain enabling its insertion into the endosomal lipid bilayer membrane to form a channel large enough to accommodate the unfolded L chain. The L chain moiety of the BoNT protein then traverses this channel towards the cytosol, the disulfide bond holding the H and L chains together is broken, and the L chain refolds and is released into the cytosol. Koriazova and Montal (2003) proposed that the "LC refolds at the interface and dissociates from the HC in the reducing cytosolic milieu where it cleaves its substrate SNAP-25".The molecular details of this process are not yet well understood.<br> PathwayStep3420 PathwayStep3421 PathwayStep3422 Pore or channel formation in endosomal membrane Conformational change in BoNT induced by pH Transportation of BoNT Light chain to cytosol