Sugar-induced conformational change found in the HA-33/HA-17 trimer of the botulinum toxin complex
Sugar-induced conformational change found in the HA-33/HA-17 trimer of the botulinum toxin complex
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在肉毒杆菌毒素复合物的 HA-33/HA-17 三聚体中发现糖诱导的构象变化
DOI：
10.1016/j.bbrc.2013.07.112
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Koichi Niwa
中科院分区：
文献类型：
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作者：
Yoshimasa Sagane;Shintaro Hayash;Takashi Matsumoto;Shin-ichro Miyashita;Ken Inui;Keita Miyata;Shunsuke Yajima;Tomonori Suzuki;Kimiko Hasegawa;Akihito Yamano;Atushi Nishikawa;Tohru Ohyama;Toshihiro Watanabe;Koichi Niwa
大尺寸肉毒杆菌毒素复合物（L-TC）由神经毒素、无毒非血凝素和血凝素（HA）复合物结合而成。 HA 复合物由三个 HA-70 分子和三个 HA-33/HA-17 三聚体结合形成，由一个 HA-17 和两个 HA-33 蛋白组成。从血清型 D L-TC 中分离出的 HA-33/HA-17 三聚体能够以唾液酸依赖性方式结合并穿透肠上皮细胞单层，因此在通过肠细胞壁的毒素递送中发挥重要作用。在本研究中，我们利用小角 X 射线散射 (SAXS) 确定了 HA-33/HA-17 三聚体的溶液结构。 HA-33/HA-17 的 SAXS 图像表现出与复合物晶体图像大致相似的外观。另一方面，在存在N-乙酰神经氨酸、葡萄糖和半乳糖的情况下，HA-33/HA-17三聚体的溶液结构与不存在糖的情况下的结构相比发生了显着改变。糖诱导的 HA-33/HA-17 三聚体结构变化可能有助于细胞结合和随后跨肠细胞层的转运。
Large-sized botulinum toxin complex (L-TC) is formed by conjugation of neurotoxin, nontoxic nonhemagglutinin and hemagglutinin (HA) complex. The HA complex is formed by association of three HA-70 molecules and three HA-33/HA-17 trimers, comprised of a single HA-17 and two HA-33 proteins. The HA-33/HA-17 trimer isolated from serotype D L-TC has the ability to bind to and penetrate through the intestinal epithelial cell monolayer in a sialic acid-dependent manner, and thus it plays an important role in toxin delivery through the intestinal cell wall. In this study, we determined the solution structure of the HA-33/HA-17 trimer by using small-angle X-ray scattering (SAXS). The SAXS image of HA-33/HA-17 exhibited broadly similar appearance to the crystal image of the complex. On the other hand, in the presence ofN-acetylneuraminic acid, glucose and galactose, the solution structure of the HA-33/HA-17 trimer was drastically altered compared to the structure in the absence of the sugars. Sugar-induced structural change of the HA-33/HA-17 trimer may contribute to cell binding and subsequent transport across the intestinal cell layer.