Crystal structure of the Rubella virus protease reveals a unique papain-like protease fold

Rubella is well-controlled due to an effective vaccine, but outbreaks are still occurring without any available antiviral treatments. There is still much to learn about the rubella virus (RUBV) papain-like protease (RubPro) that could be a potential drug target. This protease is crucial to RUBV repl...

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Bibliographic Details
Published in:bioRxiv 2022-04
Main Authors: Ezekiel Ze Ken Cheong, Quek, Jun Ping, Liu, Xin, Li, Chaoqiang, Jing Yi Chan, Liew, Chong Wai, Mu, Yuguang, Zheng, Jie, Luo, Dahai
Format: Article
Language:English
Subjects:
Conserved sequence
Crystal structure
DNA helicase
Immune response
Innate immunity
Papain
Proteinase
Replication
Rubella
Severe acute respiratory syndrome coronavirus 2
Structure-function relationships
Therapeutic targets
Viruses
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Summary:Rubella is well-controlled due to an effective vaccine, but outbreaks are still occurring without any available antiviral treatments. There is still much to learn about the rubella virus (RUBV) papain-like protease (RubPro) that could be a potential drug target. This protease is crucial to RUBV replication, cleaving the non-structural polyprotein p200 into 2 multi-functional proteins, p150 and p90. Here we report a novel crystal structure of RubPro at 1.64 Angstrom resolution. It has a similar catalytic core structure to that of SARS-CoV-2 and foot-mouth-disease virus (FMDV) proteases. RubPro has well-conserved sequence motifs that are also found in its newly discovered Rubivirus relatives. The RubPro construct was shown to have protease activity in trans against a construct of RUBV protease-helicase and fluorogenic peptide. A protease-helicase construct was also cleaved in E. coli expression. RubPro was demonstrated to possess deubiquitylation activity, suggesting a potential role of RubPro in modulating the host's innate immune responses. The structural and functional insights of the RubPro will advance our current understanding of its function and point to more structure-based research into the RUBV replication machinery, in hopes of developing antiviral therapeutics in the future. Competing Interest Statement The authors have declared no competing interest.
DOI:10.1101/2022.04.15.488536