Crystal structure of the Rubella virus protease reveals a unique papain-like protease fold
文献类型：期刊论文
| 作者 | Cheong, Ezekiel Ze Ken1,2,8; Quek, Jun Ping1,3; Xin, Liu4; Li, Chaoqiang5; Chan, Jing Yi6; Liew, Chong Wai2,3; Mu, Yuguang2; Zheng, Jie4,5,7; Luo, Dahai1,2,3 |
| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
 |
| 出版日期 | 2022-08-01 |
| 卷号 | 298期号:8页码:13 |
| DOI | 10.1016/j.jbc.2022.102250 |
| 通讯作者 | Luo, Dahai(luodahai@ntu.edu.sg) |
| 英文摘要 | Rubella, a viral disease characterized by a red skin rash, is well controlled because of an effective vaccine, but outbreaks are still occurring in the absence of available antiviral treatments. The Rubella virus (RUBV) papain-like protease (RubPro) is crucial for RUBV replication, cleaving the nonstructural polyprotein p200 into two multifunctional proteins, p150 and p90. This protease could represent a potential drug target, but structural and mechanistic details important for the inhibition of this enzyme are unclear. Here, we report a novel crystal structure of RubPro at a resolution of 1.64 angstrom. The RubPro adopts a unique papain-like protease fold, with a similar catalytic core to that of proteases from Severe acute respiratory syndrome coronavirus 2 and foot-and-mouth disease virus while having a distinctive N-terminal fingers domain. RubPro has well-conserved sequence motifs that are also found in its newly discovered Rubivirus relatives. In addition, we show that the RubPro construct has protease activity in trans against a construct of RUBV protease-helicase and fluorogenic peptides. A protease-helicase construct, exogenously expressed in Escherichia coli, was also cleaved at the p150-p90 cleavage junction, demonstrating protease activity of the protease-helicase protein. We also demonstrate that RubPro possesses deubiquitylation activity, suggesting a potential role of RubPro in modulating the host's innate immune responses. We anticipate that these structural and functional insights of RubPro will advance our current understanding of its function and help facilitate more structure-based research into the RUBV replication machinery, in hopes of developing antiviral therapeutics against RUBV. |
| WOS关键词 | NONSTRUCTURAL PROTEIN ; POLYMERASE INHIBITOR ; MOLECULAR DOCKING ; BINDING ; DOMAIN ; RNA ; REPLICATION ; REFINEMENT ; MECHANISM ; OUTBREAK |
| 资助项目 | Nanyang Presidential Graduate Scholarship ; Lee Kong Chian School of Medicine |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000916443600010 |
| 出版者 | ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/303549]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Luo, Dahai |
| 作者单位 | 1.Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore 2.Nanyang Technol Univ, Sch Biol Sci, Singapore, Singapore 3.Nanyang Technol Univ, NTU Inst Struct Biol, Singapore, Singapore 4.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China 5.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Jiangsu, Peoples R China 6.Nanyang Technol Univ, Sch Chem & Biomed Engn, Singapore, Singapore 7.UCAS, Sch Pharmaceut Sci & Technol, Hangzhou Inst Adv Study, Hangzhou, Peoples R China 8.Duke NUS Med Sch, Singapore, Singapore |
| 推荐引用方式 GB/T 7714 | Cheong, Ezekiel Ze Ken,Quek, Jun Ping,Xin, Liu,et al. Crystal structure of the Rubella virus protease reveals a unique papain-like protease fold[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2022,298(8):13. |
| APA | Cheong, Ezekiel Ze Ken.,Quek, Jun Ping.,Xin, Liu.,Li, Chaoqiang.,Chan, Jing Yi.,...&Luo, Dahai.(2022).Crystal structure of the Rubella virus protease reveals a unique papain-like protease fold.JOURNAL OF BIOLOGICAL CHEMISTRY,298(8),13. |
| MLA | Cheong, Ezekiel Ze Ken,et al."Crystal structure of the Rubella virus protease reveals a unique papain-like protease fold".JOURNAL OF BIOLOGICAL CHEMISTRY 298.8(2022):13. |
入库方式： OAI收割
来源：上海药物研究所
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