Reversible Association of the Hemagglutinin Subcomplex, HA-33/HA-17 Trimer, with the Botulinum Toxin Complex

Reversible Association of the Hemagglutinin Subcomplex, HA-33/HA-17 Trimer, with the Botulinum Toxin Complex
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血凝素亚复合物、HA-33/HA-17 三聚体与肉毒杆菌毒素复合物的可逆结合

DOI:
10.1007/s10930-017-9733-y
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发表时间:
2017
期刊:
The Protein Journal
影响因子:
--
通讯作者:
Watanabe T
Watanabe T
中科院分区:
--
文献类型:
--
作者:
Sagane Y;Mutoh S;Koizumi R;Suzuki T;Miyashita S;Miyata K;Ohyama T;Niwa K;Watanabe T

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肉毒神经毒素(BoNT)与无毒蛋白质(无毒非血凝素(NTNHA)或NTNHA与血凝素(HA)的复合物)结合形成M-或L-毒素复合物(TC)。单个BoNT和NTNHA分子缔合并形成M-TC。70 kDa HA蛋白的三聚体(HA-70)与M-TC结合形成M-TC/HA-70。此外,由1个HA-17蛋白和2个HA-33蛋白组成的1-3个臂状33-和17-kDa HA分子(HA-33/HA-17三聚体)可以附着于M-TC/HA-70复合物,产生1-、2-和3-臂L-TC。在本研究中,纯化的1-和2-臂L-TC在长期储存和冻融过程中从其他TC获得HA-33/HA-17三聚体后自发转化为另一种L-TC物质。透射电子显微镜分析提供了纯化TC制剂中形成分离的HA-33/HA-17三聚体的证据。这些发现提供了M-TC/HA-70复合物与HA-33/HA-17三聚体可逆缔合/解离以及培养物中肉毒杆菌TC四级结构动态转化的证据。
Botulinum neurotoxin (BoNT) associates with nontoxic proteins, either a nontoxic nonhemagglutinin (NTNHA) or the complex of NTNHA and hemagglutinin (HA), to form M- or L-toxin complexes (TCs). Single BoNT and NTNHA molecules are associated and form M-TC. A trimer of the 70-kDa HA protein (HA-70) attaches to the M-TC to form M-TC/HA-70. Further, 1–3 arm-like 33- and 17-kDa HA molecules (HA-33/HA-17 trimer), consisting of 1 HA-17 protein and 2 HA-33 proteins, can attach to the M-TC/HA-70 complex, yielding 1-, 2-, and 3-arm L-TC. In this study, the purified 1- and 2-arm L-TCs spontaneously converted into another L-TC species after acquiring the HA-33/HA-17 trimer from other TCs during long-term storage and freezing/thawing. Transmission electron microscopy analysis provided evidence of the formation of detached HA-33/HA-17 trimers in the purified TC preparation. These findings provide evidence of reversible association/dissociation of the M-TC/HA-70 complex with the HA-33/HA-17 trimers, as well as dynamic conversion of the quaternary structure of botulinum TC in culture.
DOI: 10.1016/j.bbrep.2016.11.008
发表时间: 2017-03
影响因子: 2.7
作者:
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影响因子: --
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发表时间: 2006-10-04
期刊: EMBO JOURNAL
影响因子: 11.4
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期刊:
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