Rossetto O, Deloye F, Poulain B, Pellizzari R, Schiavo G, Montecucco C
Centro CNR Biomembrane, Università di Padova, Italy.
J Physiol Paris. 1995;89(1):43-50. doi: 10.1016/0928-4257(96)80550-X.
Tetanus and botulinum neurotoxins are produced by several Clostridia and cause the paralytic syndromes of tetanus and botulism by blocking neurotransmitter release at central and peripheral synapses, respectively. They consist of two disulfide-linked polypeptides: H (100 kDa) is responsible for neurospecific binding and cell penetration of L (50 kDa), a zinc-endopeptidase specific for three protein subunits of the neuroexocytosis apparatus. Tetanus neurotoxin and botulinum neurotoxin serotypes B, D, F and G cleave at single sites, which differ for each neurotoxin, VAMP/synaptobrevin, a membrane protein of the synaptic vesicles. Botulinum A and E neurotoxins cleave SNAP-25, a protein of the presynaptic membrane, at two different carboxyl-terminal peptide bonds. Serotype C cleaves specifically syntaxin, another protein of the nerve plasmalemma. The target specificity of these metallo-proteinases relies on a double recognition of their substrates based on interactions with the cleavage site and with a non-contiguous segment that contains a structural motif common to VAMP, SNAP-25 and syntaxin.
破伤风毒素和肉毒杆菌神经毒素由几种梭菌产生，分别通过阻断中枢和外周突触处的神经递质释放，导致破伤风和肉毒中毒的麻痹综合征。它们由两个通过二硫键连接的多肽组成：重链（100 kDa）负责神经特异性结合以及轻链（50 kDa）的细胞穿透，轻链是一种锌内肽酶，对神经外排装置的三个蛋白质亚基具有特异性。破伤风神经毒素以及肉毒杆菌神经毒素B、D、F和G血清型在单个位点切割，每个神经毒素的切割位点不同，切割对象为囊泡相关膜蛋白/突触小泡蛋白，这是一种突触小泡的膜蛋白。肉毒杆菌A和E神经毒素在突触前膜蛋白SNAP - 25的两个不同羧基末端肽键处进行切割。C血清型特异性切割 syntaxin，这是神经质膜的另一种蛋白质。这些金属蛋白酶的靶标特异性依赖于对其底物的双重识别，这种识别基于与切割位点以及与一个不连续片段的相互作用，该片段包含囊泡相关膜蛋白、SNAP - 25和syntaxin共有的结构基序。
