Dipartimento di Scienze Biomediche and Istituto CNR di Neuroscienze, Università di Padova, Viale Ugo Bassi 58/B, 35131 Padova, Italy.
FEBS Lett. 2013 Nov 29;587(23):3831-6. doi: 10.1016/j.febslet.2013.10.010. Epub 2013 Oct 21.
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.
肉毒杆菌神经毒素通过囊泡膜转运其酶结构域。该过程的分子触发机制尚不清楚。在这里，我们测试了这个过程是否由保守表面羧酸的质子化引发。谷氨酸-48、谷氨酸-653 和天冬氨酸-877 被确定为可能的候选物，并被转化为酰胺。由于酶结构域更快地进入细胞质，这种三突变体表现出更高的神经毒性；膜易位可以在较低的 pH 值下进行。因此，特定负表面电荷的中和促进了膜接触，从而更快地启动毒素的膜插入。
