PMID- 27795409 OWN - NLM STAT- MEDLINE DCOM- 20170515 LR - 20221207 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 91 IP - 1 DP - 2017 Jan 1 TI - Structural Biology of the Arterivirus nsp11 Endoribonucleases. LID - 10.1128/JVI.01309-16 [doi] LID - e01309-16 AB - 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 euro1.5 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. CI - Copyright (c) 2016 American Society for Microbiology. FAU - Zhang, Manfeng AU - Zhang M AD - Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, China. AD - State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China. FAU - Li, Xiaorong AU - Li X AD - State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China. FAU - Deng, Zengqin AU - Deng Z AD - State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China. FAU - Chen, Zhenhang AU - Chen Z AD - State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China. FAU - Liu, Yang AU - Liu Y AD - State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China. FAU - Gao, Yina AU - Gao Y AD - State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China. FAU - Wu, Wei AU - Wu W AD - State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China. FAU - Chen, Zhongzhou AU - Chen Z AUID- ORCID: 0000-0003-1319-9664 AD - Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, China chenzhongzhou@cau.edu.cn. AD - State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China. LA - eng PT - Journal Article DEP - 20161216 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Recombinant Proteins) RN - 0 (Viral Nonstructural Proteins) RN - EC 3.1.- (Endoribonucleases) RN - EC 3.1.- (nidoviral uridylate-specific endoribonuclease) SB - IM MH - Amino Acid Sequence MH - Catalytic Domain MH - Conserved Sequence MH - Crystallography, X-Ray MH - Endoribonucleases/*chemistry/genetics/metabolism MH - Equartevirus/*chemistry/enzymology MH - Escherichia coli/genetics/metabolism MH - Gene Expression MH - Middle East Respiratory Syndrome Coronavirus/chemistry/genetics/metabolism MH - Models, Molecular MH - Mutation MH - Porcine respiratory and reproductive syndrome virus/*chemistry/enzymology MH - Protein Domains MH - Protein Multimerization MH - Protein Structure, Secondary MH - Recombinant Proteins/chemistry/genetics/metabolism MH - Severe acute respiratory syndrome-related coronavirus/chemistry/genetics/metabolism MH - Sequence Alignment MH - Viral Nonstructural Proteins/*chemistry/genetics/metabolism PMC - PMC5165224 OTO - NOTNLM OT - EAV OT - NendoU OT - PRRSV OT - arterivirus OT - crystal structures OT - flexibility OT - mutagenesis OT - nsp11 EDAT- 2016/11/01 06:00 MHDA- 2017/05/16 06:00 PMCR- 2017/06/16 CRDT- 2016/11/01 06:00 PHST- 2016/07/05 00:00 [received] PHST- 2016/10/01 00:00 [accepted] PHST- 2016/11/01 06:00 [pubmed] PHST- 2017/05/16 06:00 [medline] PHST- 2016/11/01 06:00 [entrez] PHST- 2017/06/16 00:00 [pmc-release] AID - JVI.01309-16 [pii] AID - 01309-16 [pii] AID - 10.1128/JVI.01309-16 [doi] PST - epublish SO - J Virol. 2016 Dec 16;91(1):e01309-16. doi: 10.1128/JVI.01309-16. Print 2017 Jan 1.