鉴定肉毒神经毒素 A 中突触小泡糖蛋白 2 受体结合位点。
Identification of the synaptic vesicle glycoprotein 2 receptor binding site in botulinum neurotoxin A.
机构信息
Institut für Toxikologie, OE 5340, Medizinische Hochschule Hannover, 30623 Hannover, Germany.
Institut für Toxikologie, OE 5340, Medizinische Hochschule Hannover, 30623 Hannover, Germany; Institut für Biochemie, OE 4310, Medizinische Hochschule Hannover, 30623 Hannover, Germany.
出版信息
FEBS Lett. 2014 Apr 2;588(7):1087-93. doi: 10.1016/j.febslet.2014.02.034. Epub 2014 Feb 25.
Abstract
Botulinum neurotoxins (BoNTs) inhibit neurotransmitter release by hydrolysing SNARE proteins. The most important serotype BoNT/A employs the synaptic vesicle glycoprotein 2 (SV2) isoforms A-C as neuronal receptors. Here, we identified their binding site by blocking SV2 interaction using monoclonal antibodies with characterised epitopes within the cell binding domain (HC). The site is located on the backside of the conserved ganglioside binding pocket at the interface of the HCC and HCN subdomains. The dimension of the binding pocket was characterised in detail by site directed mutagenesis allowing the development of potent inhibitors as well as modifying receptor binding properties.
摘要
肉毒神经毒素（BoNTs）通过水解 SNARE 蛋白来抑制神经递质的释放。最重要的血清型 BoNT/A 利用突触小泡糖蛋白 2（SV2）同工型 A-C 作为神经元受体。在这里，我们通过使用具有细胞结合域（HC）内特征表位的单克隆抗体阻断 SV2 相互作用来鉴定其结合位点。该位点位于保守的神经节苷脂结合口袋的背面，位于 HCC 和 HCN 亚结构域的界面上。通过定向点突变详细描述了结合口袋的尺寸，从而开发出了有效的抑制剂并改变了受体结合特性。
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