Mutagenesis of a conserved fusion peptide-like motif and membrane-proximal heptad-repeat region of hepatitis C virus glycoprotein E1
Mutagenesis of a conserved fusion peptide-like motif and membrane-proximal heptad-repeat region of hepatitis C virus glycoprotein E1
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DOI：
10.1099/vir.0.82567-0
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发表时间：
2007-04-01
影响因子：
3.8
通讯作者：
Poumbourios, Pantelis
中科院分区：
文献类型：
--
作者：
Drummer, Heidi E.;Boo, Irene;Poumbourios, Pantelis
丙型肝炎病毒E1 E2糖蛋白异源二聚体介导病毒进入。E2将病毒附着在细胞受体上;然而，E11的功能尚不清楚。我们测试了Ell是截短的II类融合蛋白的假设。我们突变的氨基酸内预测的融合肽（残基276-286）和截短的C-末端茎样基序，含有膜近端七重复序列（残基330-347）。融合肽突变F285 A消除病毒进入，而其他疏水残基的突变没有影响。丙氨酸替换七重复残基阻止进入三个五例，而取代与螺旋断路器，Pro，导致在所有情况下的入口功能丧失。突变不影响糖蛋白的表达，异源二聚体与E2或全球折叠，在原型II类融合蛋白的融合基序的突变的影响。我们的数据表明，El是不可能以类似的方式发挥作用的其他II类融合糖蛋白。
The E1E2 glycoprotein heterodimer of Hepatitis C virus mediates viral entry. E2 attaches the virus to cellular receptors; however, the function of Ell is unknown. We tested the hypothesis that Ell is a truncated class II fusion protein. We mutated amino acids within a predicted fusion peptide (residues 276-286) and a truncated C-terminal stem-like motif, containing a membrane-proximal heptad-repeat sequence (residues 330-347). The fusion peptide mutation F285A abolished viral entry, while mutation of other hydrophobic residues had no effect. Alanine replacement of heptad-repeat residues blocked entry in three of five cases, whereas substitution with the helix breaker, Pro, led to loss of entry function in all cases. The mutations did not affect glycoprotein expression, heterodimerization with E2 or global folding, in contrast to the effects of mutations in the fusion motifs of prototypical class II fusion proteins. Our data suggest that El is unlikely to function in an analogous manner to other class II fusion glycoproteins.