Association of botulinum neurotoxin serotypes A and B with synaptic vesicle protein complexes
Association of botulinum neurotoxin serotypes A and B with synaptic vesicle protein complexes
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DOI：
10.1021/bi602396x
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发表时间：
2007-03-20
期刊：
影响因子：
2.9
通讯作者：
Barbieri, Joseph T.
中科院分区：
文献类型：
--
作者：
Baldwin, Michael R.;Barbieri, Joseph T.
肉毒神经毒素（BoNT）通过切割周围神经元内的SNARE蛋白引起弛缓性麻痹。BoNT有七种血清型，称为A-G，它们在SNARE蛋白和/或切割位点上不同。BoNT是单链毒素，其包含与C-末端易位/受体结合结构域二硫键连接的N-末端锌金属蛋白酶结构域。SV 2和突触结合蛋白已分别被鉴定为BoNT血清型A和B的受体。使用亲和层析，观察到BoNTs A和B结合突触体裂解物中的突触囊泡蛋白复合物。串联LC-MS/MS鉴定SV 2、突触结合蛋白I、突触泡蛋白、囊泡相关膜蛋白2（VAMP 2）和空泡质子泵为BoNT-受体复合物的组分。密度梯度分析表明，BoNT血清型A和B表现出独特的相互作用与突触囊泡蛋白复合物。BoNT血清型A和B与突触囊泡蛋白复合物的关联暗示了蛋白复合物在突触囊泡生物学中的生理作用，并提供了对BoNT和神经元受体相互作用的了解。
Botulinum neurotoxins (BoNTs) elicit flaccid paralysis through cleavage of SNARE proteins within peripheral neurons. There are seven serotypes of the BoNTs, termed A-G, which differ in the SNARE protein and/or site that is cleaved. BoNTs are single-chain toxins that comprise an N-terminal zinc metalloprotease domain that is disulfide linked to the C-terminal translocation/receptor binding domain. SV2 and synaptotagmin have been identified as receptors for BoNT serotypes A and B, respectively. Using affinity chromatography, BoNTs A and B were observed to bind synaptic vesicle protein complexes in synaptosome lysates. Tandem LC-MS/MS identified SV2, synaptotagmin I, synaptophysin, vesicle-associated membrane protein 2 (VAMP2), and the vacuolar proton pump as components of the BoNT-receptor complex. Density gradient analysis showed that BoNT serotypes A and B exhibited unique interactions with the synaptic vesicle protein complexes. The association of BoNT serotypes A and B with synaptic vesicle protein complexes implicates a physiological role for protein complexes in synaptic vesicle biology and provides insight into the interactions of BoNT and neuronal receptors.