Howard Hughes Medical Institute.
Biochemistry. 2012 Jul 17;51(28):5655-62. doi: 10.1021/bi3004928. Epub 2012 Jul 2.
Botulinum neurotoxins (BoNTs, serotypes A-G) are the most deadly substances known. Here, we investigated how BoNT/E, a serotype that causes human botulism, translocates into the cytosol of neurons. Analogous to BoNT/B, BoNT/E required binding of the coreceptor, GT1b, to undergo significant secondary structural changes and transform into a hydrophobic protein at low pH. These data indicate that both serotypes act as coincidence detectors for both GT1b and low pH, to undergo translocation. However, BoNT/E translocated much more rapidly than BoNT/B. Also, BoNT/E required only GT1b, and not low pH, to oligomerize, whereas BoNT/B required both. In further contrast to the case of BoNT/B, low pH alone altered the secondary structure of BoNT/E to some degree and resulted in its premature inactivation. Hence, comparison of two BoNT serotypes revealed that these agents exhibit both convergent and divergent responses to receptor interactions, and pH, in the translocation pathway.
肉毒神经毒素（BoNTs，血清型 A-G）是已知最致命的物质。在这里，我们研究了导致人类肉毒中毒的血清型 BoNT/E 如何易位到神经元的细胞质中。与 BoNT/B 类似，BoNT/E 需要结合辅助受体 GT1b 才能发生显著的二级结构变化，并在低 pH 值下转化为疏水性蛋白。这些数据表明，两种血清型都充当 GT1b 和低 pH 值的巧合检测器，以进行易位。然而，BoNT/E 的易位速度明显快于 BoNT/B。此外，BoNT/E 只需 GT1b 即可寡聚，而不需要低 pH 值，而 BoNT/B 则需要两者。与 BoNT/B 的情况进一步相反，单独的低 pH 值会在某种程度上改变 BoNT/E 的二级结构，并导致其过早失活。因此，两种 BoNT 血清型的比较表明，这些因子在易位途径中对受体相互作用和 pH 值表现出既有趋同又有发散的反应。
