Structural basis of Zika virus helicase in recognizing its substrates.
Structural basis of Zika virus helicase in recognizing its substrates.
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寨卡病毒解旋酶识别底物的结构基础
DOI：
10.1007/s13238-016-0293-2
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发表时间：
2016-08
期刊：
影响因子：
21.1
通讯作者：
Rao Z
中科院分区：
文献类型：
--
作者：
Tian H;Ji X;Yang X;Zhang Z;Lu Z;Yang K;Chen C;Zhao Q;Chi H;Mu Z;Xie W;Wang Z;Lou H;Yang H;Rao Z
据报道，最近在南美洲、中美洲和加勒比地区爆发了寨卡病毒感染。与ZIKV感染相关的新生儿小头畸形已引起国际关注的公共卫生紧急情况。目前还没有治疗寨卡病毒感染的特定疫苗或药物。ZIKV解旋酶在病毒RNA复制中起着关键作用，是一个有吸引力的治疗靶点。我们测定了ZIKV解旋酶-ATP-Mn2+和ZIKV解旋酶-RNA的晶体结构。这是黄病毒解旋酶与三磷酸腺苷结合的第一个结构。与相关的黄病毒解旋酶的比较表明，尽管活性部位的关键P-环在不同物种之间具有不同的构象，但它对ATP/Mn2+的识别采用相同的模式。ZIKV解旋酶-RNA的结构表明，当RNA结合时，运动域的旋转可以引起显著的构象变化。值得注意的是，尽管ZIKV和登革病毒(DENV)的脱辅酶解旋酶都有与RNA结合的保守残基，但它们不同的运动域旋转方式导致了不同的RNA识别模式。这表明，黄病毒解旋酶可能进化出一种保守的引擎，将化学能从核苷三磷酸转化为RNA解离所需的机械能，但不同的运动域旋转导致不同的RNA识别模式，以适应病毒的个体复制。
The recent explosive outbreak of Zika virus (ZIKV) infection has been reported in South and Central America and the Caribbean. Neonatal microcephaly associated with ZIKV infection has already caused a public health emergency of international concern. No specific vaccines or drugs are currently available to treat ZIKV infection. The ZIKV helicase, which plays a pivotal role in viral RNA replication, is an attractive target for therapy. We determined the crystal structures of ZIKV helicase-ATP-Mn2+and ZIKV helicase-RNA. This is the first structure of any flavivirus helicase bound to ATP. Comparisons with related flavivirus helicases have shown that although the critical P-loop in the active site has variable conformations among different species, it adopts an identical mode to recognize ATP/Mn2+. The structure of ZIKV helicase-RNA has revealed that upon RNA binding, rotations of the motor domains can cause significant conformational changes. Strikingly, although ZIKV and dengue virus (DENV) apo-helicases share conserved residues for RNA binding, their different manners of motor domain rotations result in distinct individual modes for RNA recognition. It suggests that flavivirus helicases could have evolved a conserved engine to convert chemical energy from nucleoside triphosphate to mechanical energy for RNA unwinding, but different motor domain rotations result in variable RNA recognition modes to adapt to individual viral replication.