Protein & Cell >

2016 , Vol. 7 >Issue 8: 562 - 570

DOI: https://doi.org/10.1007/s13238-016-0293-2

RESEARCH ARTICLE

Structural basis of Zika virus helicase in recognizing its substrates

  • Hongliang Tian 1,2 ,
  • Xiaoyun Ji 3 ,
  • Xiaoyun Yang 1 ,
  • Zhongxin Zhang 4 ,
  • Zuokun Lu 5 ,
  • Kailin Yang 6 ,
  • Cheng Chen 1 ,
  • Qi Zhao 7 ,
  • Heng Chi 1 ,
  • Zhongyu Mu 1 ,
  • Wei Xie 1 ,
  • Zefang Wang 1 ,
  • Huiqiang Lou 4 ,
  • Haitao Yang , 1,2 ,
  • Zihe Rao 5
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  • 1. School of Life Sciences, Tianjin University, Tianjin 300072, China
  • 2. Tianjin International Joint Academy of Biotechnology and Medicine, Tianjin 300457, China
  • 3. The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China
  • 4. State Key Laboratory of Agro-Biotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China
  • 5. College of Life Sciences, Nankai University, Tianjin 300071, China
  • 6. Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA
  • 7. Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA

Received date: 15 Jun 2016

Accepted date: 29 Jun 2016

Published date: 12 Sep 2016

Copyright

2016 The Author(s) 2016. This article is published with open access at Springerlink.com and journal.hep.com.cn
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Abstract

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

Cite this article

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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