Building-block architecture of botulinum toxin complex: Conformational changes provide insights into the hemagglutination ability of the complex.
Building-block architecture of botulinum toxin complex: Conformational changes provide insights into the hemagglutination ability of the complex.
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DOI：
10.1016/j.bbrep.2016.11.008
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发表时间：
2017-03
影响因子：
2.7
通讯作者：
Watanabe T
中科院分区：
文献类型：
--
作者：
Suzuki T;Sagane Y;Matsumoto T;Hasegawa K;Yamano A;Niwa K;Watanabe T
肉毒梭菌产生肉毒杆菌神经毒素(BONT)。以前，我们为肉毒毒素复合体(TC)的“积木”模型提供了证据。在该模型中，单个BoNT与一个无毒的非血凝素结合，产生M-TC；三个HA-70分子连接形成M-TC/HA-70，一到三个HA-33/HA-17三聚体(两个HA-33和一个HA-17)通过HA-17和HA-17结合进一步与M-TC/HA-70结合，产生一、二和三臂L-TC。在所有的TC中，只有三臂L-TC引起了血凝。在这项研究中，我们用小角X射线散射(SAXS)确定了肉毒杆菌TCS的溶液结构。在透射电子显微镜下，成熟的三臂L-TC呈现出一只展开翅膀的鸟的形状，而不是模型有三个“臂”。SAXS图像显示，HA-33/HA-17三聚体的三个臂中的一个与HA-70和BONT结合。综上所述，这些关于TC积木结构构象变化的发现可能解释了为什么只有三臂L-TC表现出血凝。我们用SAXS研究了肉毒杆菌TCS的结构。成熟的三臂L-TC展示了一只正在展翅的小鸟的形状。HA-33/HA-17三聚体与HA-70和BONT结合的三个臂之一。这种积木结构可以解释三臂L-TC的血凝现象。
Clostridium botulinum produces the botulinum neurotoxin (BoNT). Previously, we provided evidence for the “building-block” model of botulinum toxin complex (TC). In this model, a single BoNT is associated with a single nontoxic nonhemagglutinin (NTNHA), yielding M-TC; three HA-70 molecules are attached and form M-TC/HA-70, and one to three “arms” of the HA-33/HA-17 trimer (two HA-33 and one HA-17) further bind to M-TC/HA-70 via HA-17 and HA-70 binding, yielding one-, two-, and three-arm L-TC. Of all TCs, only the three-arm L-TC caused hemagglutination. In this study, we determined the solution structures for the botulinum TCs using small-angle X-ray scattering (SAXS). The mature three-arm L-TC exhibited the shape of a “bird spreading its wings”, in contrast to the model having three “arms”, as revealed by transmission electron microscopy. SAXS images indicated that one of the three arms of the HA-33/HA-17 trimer bound to both HA-70 and BoNT. Taken together, these findings regarding the conformational changes in the building-block architecture of TC may explain why only three-arm L-TC exhibited hemagglutination. We examined the structures of botulinum TCs using SAXS. The mature three-arm L-TC exhibited the shape of a “bird spreading its wings”. One of the three arms of the HA-33/HA-17 trimer bound to both HA-70 and BoNT. The building-block architecture may explain hemagglutination by the three-arm L-TC.