botulinum neurotoxin heavy chain belt as an intramolecular chaperone for the light chain肉毒神经毒素重链带作为一个分子内伴侣蛋白轻链.pdfVIP

Opinion Botulinum Neurotoxin Heavy Chain Belt as an Intramolecular Chaperone for the Light Chain * * Axel T. Brunger , Mark A. Breidenbach, Rongsheng Jin, Audrey Fischer, Jose S. Santos, Mauricio Montal Background [18–20]. Indeed, the X-ray structure of BoNT/A-LC in complex with sn2 [16]—the C-terminal residues 141–204 of Botulism is a neuroparalytic illness caused by botulinum BoNT/A substrate SNAP-25—revealed an extensive array of neurotoxin (BoNT). Seven BoNT serotypes (designated as A substrate binding sites distant from the active site (exosites) to G) are produced by Clostridium botulinum, a spore-forming, that orient the substrate onto the vicinity of the active site obligate anaerobic bacterium. BoNT, widely considered the and determine the target specificity [16,21]. most potent toxin known and a major bioweapon [1], is a A key step for intoxication is the translocation of potent blocker of synaptic transmission in peripheral endocytosed toxin across intracellular membranes to reach cholinergic nervous system synapses, thereby causing its cytosolic targets [3]. The HC likely acts as both a channel paralysis. Based on i