Structural basis of Zika virus helicase in recognizing its substrates
Received date: 15 Jun 2016
Accepted date: 29 Jun 2016
Published date: 12 Sep 2016
Copyright
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.
Key words: Zika virus; helicase; ATP; crystal structure; flavivirus
Hongliang Tian , Xiaoyun Ji , Xiaoyun Yang , Zhongxin Zhang , Zuokun Lu , Kailin Yang , Cheng Chen , Qi Zhao , Heng Chi , Zhongyu Mu , Wei Xie , Zefang Wang , Huiqiang Lou , Haitao Yang , Zihe Rao . Structural basis of Zika virus helicase in recognizing its substrates[J]. Protein & Cell, 2016 , 7(8) : 562 -570 . DOI: 10.1007/s13238-016-0293-2
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