The pH sensor for flavivirus membrane fusion.

The pH sensor for flavivirus membrane fusion.
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DOI:
10.1083/jcb.200809175
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发表时间:
2008-10-20
影响因子:
7.8
通讯作者:
Harrison, Stephen C.
Harrison, Stephen C.
中科院分区:
生物学1区
文献类型:
--
作者:
Harrison, Stephen C.

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通过内体摄取感染细胞的病毒通常已经进化为“感知”局部pH,作为它们渗透到胞质溶胶中的机制的一部分。即使对于包膜病毒的充分研究的融合蛋白,特异性pH传感器的鉴定也是一个挑战,Fritz等人(Fritz,R.,K. Stiasny和F.X.海因茨。2008. 183:353-361)。彻底的突变分析保守的组氨酸残基的蜱传脑炎病毒的包膜蛋白,导致确定一个组氨酸的关键结构域界面的关键pH传感器,其质子化触发大规模的构象重排,诱导病毒和内体膜的融合。
Viruses that infect cells by uptake through endosomes have generally evolved to “sense” the local pH as part of the mechanism by which they penetrate into the cytosol. Even for the very well studied fusion proteins of enveloped viruses, identification of the specific pH sensor has been a challenge, one that has now been met successfully, for flaviviruses, by Fritz et al. (Fritz, R., K. Stiasny, and F.X. Heinz. 2008. J. Cell Biol. 183:353–361) in this issue. Thorough mutational analysis of conserved histidine residues in the envelope protein of tick-borne encephalitis virus led to identify a histidine at a key domain interface as the critical pH sensor; its protonation triggers the large-scale conformational rearrangement that induces fusion of viral and endosomal membranes.
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