title: The nucleoprotein of severe fever with thrombocytopenia syndrome virus processes a stable hexameric ring to facilitate RNA encapsidation.
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 Å resolution and demonstrate the mechanism by which it processes a ringshaped hexameric form to accomplish RNA encapsidation. Key residues essential for oligomerization are identified through mutational analysis and identified to have a significant impact on RNA binding, which suggests that correct formation of highly ordered oligomers is a critical step in RNA encapsidation. The findings of this work provide new insights into the discovery of new antiviral reagents for Phlebovirus infection.
authors.affiliation: College of Pharmacy and State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China.
authors.forename: Honggang
authors.initials: H
authors.lastname: Zhou
authors.forename: Yuna
authors.initials: Y
authors.lastname: Sun
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.forename: Wenming
authors.initials: W
authors.lastname: Wang
authors.forename: Xiang
authors.initials: X
authors.lastname: Liu
authors.forename: Le
authors.initials: L
authors.lastname: Li
authors.forename: Fei
authors.initials: F
authors.lastname: Deng
authors.forename: Hualin
authors.initials: H
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Guo
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Lou
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D009154:Mutation; D019590:Nucleocapsid Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016856:Phlebovirus / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D012367:RNA, Viral / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics
chemical_list: D019590:Nucleocapsid Proteins; D012367:RNA, Viral; D011994:Recombinant Proteins