Botulinum neurotoxins B and E translocate at different rates and exhibit divergent responses to GT1b and low pH.
Botulinum neurotoxins B and E translocate at different rates and exhibit divergent responses to GT1b and low pH.
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DOI：
10.1021/bi3004928
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发表时间：
2012-07-17
期刊：
影响因子：
2.9
通讯作者：
Chapman ER
中科院分区：
文献类型：
--
作者：
Sun S;Tepp WH;Johnson EA;Chapman ER
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.
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