Structural basis of Zika virus helicase in recognizing its substrates

doi:10.1007/s13238-016-0293-2

Protein Cell

2016, Vol. 7

Issue (8) : 562-570 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 Ji³,Xiaoyun Yang¹,Zhongxin Zhang⁴,Zuokun Lu⁵,Kailin Yang⁶,Cheng Chen¹,Qi Zhao⁷,Heng Chi¹,Zhongyu Mu¹,Wei Xie¹,Zefang Wang¹,Huiqiang Lou⁴,Haitao Yang^1,²(

),Zihe Rao⁵

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

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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.

Keywords Zika virus helicase ATP crystal structure flavivirus

Corresponding Author(s): Haitao Yang

Issue Date: 12 September 2016

Cite this article:

Hongliang Tian,Xiaoyun Ji,Xiaoyun Yang, et al. Structural basis of Zika virus helicase in recognizing its substrates[J]. Protein Cell, 2016, 7(8): 562-570.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-016-0293-2
https://academic.hep.com.cn/pac/EN/Y2016/V7/I8/562

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