Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institute, 5232 Villigen PSI, Switzerland.
Department of Chemistry and Applied Biosciences, RETHINK, ETH Zurich, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland.
Toxicon. 2020 Feb;175:36-43. doi: 10.1016/j.toxicon.2019.11.010. Epub 2019 Nov 26.
A dual-receptor interaction with a polysialoganglioside and synaptic vesicle glycoprotein 2 (SV2) is required for botulinum neurotoxin A (BoNT) toxicity. Here, we review what is currently known about the BoNT/A-SV2 interaction based on structural studies. Currently, five crystal structures of the receptor-binding domain (Hc) of BoNT subtypes A1 and A2 complexed to the large luminal domain (LD4) of SV2C have been determined. On the basis of the available structures, we will discuss the importance of protein-protein and protein-carbohydrate interactions for BoNT/A toxicity as well as the high plasticity of BoNT/A for receptor recognition by tolerating a variety of side-chain interactions at the interface. A plausible explanation how receptor-binding specificity of BoNT/A may be achieved without an extensive and conserved side chain-side chain interaction network will be provided.
双受体相互作用与多唾液酸神经节苷脂和突触囊泡糖蛋白 2（SV2）是肉毒杆菌神经毒素 A（BoNT/A）毒性所必需的。在这里，我们根据结构研究综述了目前已知的 BoNT/A-SV2 相互作用。目前，已经确定了 BoNT 亚型 A1 和 A2 的受体结合域（Hc）与 SV2C 的大腔域（LD4）复合的五个晶体结构。基于现有的结构，我们将讨论蛋白质-蛋白质和蛋白质-碳水化合物相互作用对于 BoNT/A 毒性的重要性，以及 BoNT/A 对受体识别的高可塑性，通过容忍界面处的各种侧链相互作用。我们将提供一个合理的解释，说明 BoNT/A 的受体结合特异性如何在没有广泛而保守的侧链-侧链相互作用网络的情况下实现。
