The role of histidine residues in low-pH-mediated viral membrane fusion
The role of histidine residues in low-pH-mediated viral membrane fusion
复制标题
DOI：
10.1016/j.str.2006.07.011
复制
发表时间：
2006-10-01
期刊：
影响因子：
5.7
通讯作者：
Kobe, Bostjan
中科院分区：
文献类型：
--
作者：
Kampmann, Thorsten;Mueller, Daniela S.;Kobe, Bostjan
被包裹的病毒入侵宿主细胞的一个中心事件是病毒和细胞膜的融合。对于许多病毒来说，膜融合是由特定的病毒表面蛋白驱动的，这些蛋白经历了大规模的构象重排，内吞体内暴露于低pH值后触发了这些重排。在这里，我们提出的证据表明，在I类(螺旋发夹蛋白)和11类(富含β结构的蛋白)的pH依赖的融合蛋白中，特定组氨酸残基的质子化通过类似的分子机制触发融合。这些组氨酸位于融合前构象中带正电荷的残基附近，随后与融合后构象中带负电荷的残基形成盐桥。导致融合的相应结构重排所涉及的分子表面是高度保守的，因此可能为抗病毒药物的设计提供一个合适的共同靶点，这些药物可能对多种致病病毒具有活性。
A central event in the invasion of a host cell by an enveloped virus is the fusion of viral and cell membranes. For many viruses, membrane fusion is driven by specific viral surface proteins that undergo large-scale conformational rearrangements, triggered by exposure to low pH in the endosome upon internalization. Here, we present evidence suggesting that in both class I (helical hairpin proteins) and class 11 (beta-structure-rich proteins) pH-dependent fusion proteins the protonation of specific histidine residues triggers fusion via an analogous molecular mechanism. These histidines are located in the vicinity of positively charged residues in the prefusion conformation, and they subsequently form salt bridges with negatively charged residues in the postfusion conformation. The molecular surfaces involved in the corresponding structural rearrangements leading to fusion are highly conserved and thus might provide a suitable common target for the design of antivirals, which could be active against a diverse range of pathogenic viruses.