The nucleoprotein of severe fever with thrombocytopenia syndrome virus processes a stable hexameric ring to facilitate RNA encapsidation

doi:10.1007/s13238-013-3901-4

Prot Cell

2013, Vol. 4

Issue (6) : 445-455 https://doi.org/10.1007/s13238-013-3901-4 PMID: 23702688

RESEARCH ARTICLE

The nucleoprotein of severe fever with thrombocytopenia syndrome virus processes a stable hexameric ring to facilitate RNA encapsidation

Honggang Zhou^1,2, Yuna Sun⁴, Ying Wang⁵, Min Liu^1,5, Chao Liu^1,5, Wenming Wang^1,5, Xiang Liu⁵, Le Li^1,5, Fei Deng³, Hualin Wang³(

), Yu Guo¹(

), Zhiyong Lou²(

)

1. College of Pharmacy and State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China; 2. Laboratory of Structural Biology and MOE Laboratory of Protein Science, School of Medicine and Life Sciences, Tsinghua University, Beijing 100084, China; 3. State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; 4. National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing 100101, China; 5. High-throughput Molecular Drug Discovery Center, Tianjin Joint Academy of Biotechnology and Medicine, Tianjin 300457, China

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Abstract

Severe fever with thrombocytopenia syndrome virus (SFTSV), a member of the Phlebovirus genus from the Bunyaviridae family endemic to China, is the causative agent of life-threatening severe fever with thrombocytopenia syndrome (SFTS), which features high fever and hemorrhage. Similar to other negative-sense RNA viruses, SFTSV encodes a nucleocapsid protein (NP) that is essential for viral replication. NP facilitates viral RNA encapsidation and is responsible for the formation of ribonucleoprotein complex. However, recent studies have indicated that NP from Phlebovirus members behaves in inhomogeneous oligomerization states. In the present study, we report the crystal structure of SFTSV NP at 2.8 ? resolution and demonstrate the mechanism by which it processes a ringshaped hexameric form to accomplish RNA encapsidation. Key residues essential for oligomerization are identifi ed through mutational analysis and identifi ed to have a signifi cant impact on RNA binding, which suggests that correct formation of highly ordered oligomers is a critical step in RNA encapsidation. The fi ndings of this work provide new insights into the discovery of new antiviral reagents for Phlebovirus infection.

Keywords SFTSV nucleoprotein oligomer RNP as-KEYWORDS sembly crystal structure

Corresponding Author(s): Wang Hualin,Email:h.wang@wh.iov.cn; Guo Yu,Email:guoyu@nankai.edu.cn; Lou Zhiyong,Email:louzy@xtal.tsinghua.edu.cn

Issue Date: 01 June 2013

Cite this article:

Honggang Zhou,Yuna Sun,Xiang Liu, et al. The nucleoprotein of severe fever with thrombocytopenia syndrome virus processes a stable hexameric ring to facilitate RNA encapsidation[J]. Prot Cell, 2013, 4(6): 445-455.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-013-3901-4
https://academic.hep.com.cn/pac/EN/Y2013/V4/I6/445

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