Molecular Assembly of Clostridium botulinum progenitor M complex of type E.
Molecular Assembly of Clostridium botulinum progenitor M complex of type E.
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DOI：
10.1038/srep17795
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发表时间：
2015-12-07
影响因子：
4.6
通讯作者：
Swaminathan S
中科院分区：
文献类型：
--
作者：
Eswaramoorthy S;Sun J;Li H;Singh BR;Swaminathan S
肉毒杆菌神经毒素（BoNT）作为一种前体复合物释放，与一种无毒的非血凝素蛋白（NTNH）和其他相关蛋白相关。我们已经确定了肉毒杆菌神经毒素E [PTC-E(M)]的M型祖复合物的晶体结构，这是BoNT和NTNH的异源二聚体。晶体结构表明，该配合物是BoNT和NTNH紧密互锁的异源二聚体。晶体结构解释了分子组装的机制，并揭示了界面上的几个酸性团簇负责低酸性pH下的结合和碱性/中性pH下的解离。PTC-E(M)和先前确定的PTC-A(M)之间的一般结构的相似性强烈表明，所有肉毒杆菌血清型的祖先M复合物可能具有相似的分子排列。尽管当神经毒素从M复合物释放出来时，它们的形态明显不同。
Clostridium botulinum neurotoxin (BoNT) is released as a progenitor complex, in association with a non-toxic-non-hemagglutinin protein (NTNH) and other associated proteins. We have determined the crystal structure of M type Progenitor complex of botulinum neurotoxin E [PTC-E(M)], a heterodimer of BoNT and NTNH. The crystal structure reveals that the complex exists as a tight, interlocked heterodimer of BoNT and NTNH. The crystal structure explains the mechanism of molecular assembly of the complex and reveals several acidic clusters at the interface responsible for association at low acidic pH and disassociation at basic/neutral pH. The similarity of the general architecture between the PTC-E(M) and the previously determined PTC-A(M) strongly suggests that the progenitor M complexes of all botulinum serotypes may have similar molecular arrangement, although the neurotoxins apparently can take very different conformation when they are released from the M complex.