Neutralisation of specific surface carboxylates speeds up translocation of botulinum neurotoxin type B enzymatic domain
Neutralisation of specific surface carboxylates speeds up translocation of botulinum neurotoxin type B enzymatic domain
复制标题
DOI：
10.1016/j.febslet.2013.10.010
复制
发表时间：
2013-11-29
期刊：
影响因子：
3.5
通讯作者：
Binz, Thomas
中科院分区：
文献类型：
--
作者：
Pirazzini, Marco;Henke, Tina;Binz, Thomas
植物神经毒素将其酶结构域转移穿过囊泡膜。这个过程的分子触发器是未知的。在这里，我们测试的可能性，这是由保守的表面羧酸质子化引起的。谷氨酸-48、谷氨酸-653和天冬氨酸-877被鉴定为可能的候选物，并被转化为酰胺。这三重突变体表现出增加的神经毒性，由于更快的胞质传递的酶结构域;膜易位可以发生在酸性较低的pH值。因此，特定的负表面电荷的中和有利于膜接触，允许更快地启动毒素膜插入。(C)2013年欧洲生物化学学会联合会。由Elsevier B出版。V.保留所有权利。
Botulinum neurotoxins translocate their enzymatic domain across vesicular membranes. The molecular triggers of this process are unknown. Here, we tested the possibility that this is elicited by protonation of conserved surface carboxylates. Glutamate-48, glutamate-653 and aspartate-877 were identified as possible candidates and changed into amide. This triple mutant showed increased neurotoxicity due to faster cytosolic delivery of the enzymatic domain; membrane translocation could take place at less acidic pH. Thus, neutralisation of specific negative surface charges facilitates membrane contact permitting a faster initiation of the toxin membrane insertion. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.