Structural Biology of the Arterivirus nsp11 Endoribonucleases
Structural Biology of the Arterivirus nsp11 Endoribonucleases
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动脉病毒 nsp11 核糖核酸内切酶的结构生物学
DOI：
10.1128/jvi.01309-16
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发表时间：
2016-10
影响因子：
5.4
通讯作者：
Chen Zhongzhou
中科院分区：
文献类型：
--
作者：
Liu Yang;Gao Yina;Wu Wei;Chen Zhongzhou
摘要核糖核酸内切酶（NendoU）是一种独特而保守的主要遗传标记，在脊椎动物宿主的巢状病毒。动脉炎病毒非结构蛋白11（nsp 11）被证明具有NendoU活性，并在病毒的生命周期中发挥重要作用。在这里，我们报告了三个晶体结构的猪繁殖与呼吸综合征病毒（PRRSV）和马动脉炎病毒（EAV）nsp 11突变体。动脉炎病毒nsp 11的结构包含两个保守的紧凑结构域：N-末端结构域（NTD）和C-末端结构域（CTD）。在动脉炎病毒中，PRRSV和EAV的核糖核酸内切酶结构相似且保守，但它们与严重急性呼吸综合征（SARS）和中东呼吸综合征（MERS）冠状病毒（CoV）的结构有很大不同，后者代表了巢状病毒目中重要的人类病原体。NendoU活性的催化中心位于CTD中，其中带正电荷的沟靠近巢病毒中保守的关键催化残基。虽然NTD几乎相同，动脉炎病毒nsp 11家族蛋白的催化区域是非常灵活的，寡聚化可能是浓度依赖性的。总之，我们的结构为这个关键的多功能NendoU蛋白家族提供了新的见解，并为更好地理解分子机制和抗病毒药物开发奠定了基础。重要性猪繁殖与呼吸综合征病毒（PRRSV）和马动脉炎病毒是动脉炎病毒家族的两个主要成员。猪繁殖与呼吸综合征病毒（PRRSV）是一种主要的猪病原体，可引起种猪繁殖障碍和仔猪呼吸道疾病。由于缺乏合适的疫苗或有效的药物治疗以及这些病毒的快速传播，受感染的动物要么很快死亡，要么必须被扑杀。PRRSV在美国每年给养猪业造成约6.44亿美元的损失，在欧洲每年约15亿欧元。为了找到一种对抗这些病毒的方法，我们将重点放在了重要的病毒非结构蛋白11（nsp 11）上。nsp 11与多种功能相关，如RNA加工和抑制感染宿主的先天免疫系统。这项研究中解决的三种结构为这个关键蛋白质家族的分子机制提供了新的见解，并将有利于开发针对这些致命病毒的新疗法。
ABSTRACT Endoribonuclease (NendoU) is unique and conserved as a major genetic marker in nidoviruses that infect vertebrate hosts. Arterivirus nonstructural protein 11 (nsp11) was shown to have NendoU activity and play essential roles in the viral life cycle. Here, we report three crystal structures of porcine reproductive and respiratory syndrome virus (PRRSV) and equine arteritis virus (EAV) nsp11 mutants. The structures of arterivirus nsp11 contain two conserved compact domains: the N-terminal domain (NTD) and C-terminal domain (CTD). The structures of PRRSV and EAV endoribonucleases are similar and conserved in the arterivirus, but they are greatly different from that of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoV), representing important human pathogens in the Nidovirales order. The catalytic center of NendoU activity is located in the CTD, where a positively charged groove is next to the key catalytic residues conserved in nidoviruses. Although the NTD is nearly identical, the catalytic region of the arterivirus nsp11 family proteins is remarkably flexible, and the oligomerization may be concentration dependent. In summary, our structures provide new insight into this key multifunctional NendoU family of proteins and lay a foundation for better understanding of the molecular mechanism and antiviral drug development. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) and equine arteritis virus are two major members of the arterivirus family. PRRSV, a leading swine pathogen, causes reproductive failure in breeding stock and respiratory tract illness in young pigs. Due to the lack of a suitable vaccine or effective drug treatment and the quick spread of these viruses, infected animals either die quickly or must be culled. PRRSV costs the swine industry around $644 million annually in the United States and almost €1.5 billion in Europe every year. To find a way to combat these viruses, we focused on the essential viral nonstructural protein 11 (nsp11). nsp11 is associated with multiple functions, such as RNA processing and suppression of the infected host innate immunity system. The three structures solved in this study provide new insight into the molecular mechanisms of this crucial protein family and will benefit the development of new treatments against these deadly viruses.
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DOI：
10.1080/1044667031000137575
发表时间：
2002-09
期刊：
Developmental immunology
影响因子：
--
作者：
Selmi C;Ansari AA;Invernizzi P;Podda M;Gershwin ME
通讯作者：
Gershwin ME
影响因子：
6.7
作者：
The PLOS Pathogens Staff
通讯作者：
The PLOS Pathogens Staff
影响因子：
5
作者：
Gorbalenya AE;Enjuanes L;Ziebuhr J;Snijder EJ
通讯作者：
Snijder EJ
影响因子：
64.8
作者：
H. Lipson
通讯作者：
H. Lipson
DOI：
10.1107/s0907444999000839
发表时间：
1999-04
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Terwilliger TC;Berendzen J
通讯作者：
Berendzen J