NS4A regulates the ATPase activity of the NS3 helicase: a novel cofactor role of the non-structural protein NS4A from West Nile virus
NS4A regulates the ATPase activity of the NS3 helicase: a novel cofactor role of the non-structural protein NS4A from West Nile virus
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DOI：
10.1099/vir.0.012864-0
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发表时间：
2009-09-01
影响因子：
3.8
通讯作者：
Strongin, Alex Y.
中科院分区：
文献类型：
--
作者：
Shiryaev, Sergey A.;Chernov, Andrei V.;Strongin, Alex Y.
使用编码单独的西尼罗病毒（WNV）NS 3解旋酶（NS 3 hel）和连接至NS 4A的亲水性N-末端1-50序列的NS 3 hel的构建体，我们证明了NS 4A的存在允许NS 3 hel在寡核苷酸底物解旋过程中保存能量。使用NS 4A突变体，我们还确定了NS 4A的C-末端酸性EELPD/E基序，其似乎在功能上类似于丙型肝炎病毒（HCV）NS 4A的酸性EFDE基序，对于调节NS 3 hel的ATP酶活性是必需的。我们得出结论，类似于HCV NS 4A，WNV的NS 4A作为NS 3 hel的辅因子，并允许解旋酶在ATIP缺陷的条件下维持病毒RNA的解旋速率。
Using constructs that encode the individual West Nile virus (WNV) NS3helicase (NS3hel) and NS3hel linked to the hydrophilic, N-terminal 1-50 sequence of NS4A, we demonstrated that the presence of NS4A allows NS3hel to conserve energy in the course of oligonucleotide substrate unwinding. Using NS4A mutants, we also determined that the C-terminal acidic EELPD/E motif of NS4A, which appears to be functionally similar to the acidic EFDEMEE motif of hepatitis C virus (HCV) NS4A, is essential for regulating the ATPase activity of NS3hel. We concluded that, similar to HCV NS4A, NS4A of WNV acts as a cofactor for NS3hel and allows helicase to sustain the unwinding rate of the viral RNA under conditions of ATIP deficiency.