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Publication Abstract from PubMed

Rubella, a viral disease characterized by a red skin rash, is well-controlled due to 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 non-structural polyprotein p200 into two multi-functional 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 1.64 A resolution. The RubPro adopts a unique papain-like protease fold, with a similar catalytic core to that of proteases from SARS-CoV-2 and foot-mouth-disease virus (FMDV) 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 E. 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 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.

Crystal structure of the Rubella virus protease reveals a unique papain-like protease fold.,Cheong EZK, Quek JP, Xin L, Li C, Chan JY, Liew CW, Mu Y, Zheng J, Luo D J Biol Chem. 2022 Jul 11:102250. doi: 10.1016/j.jbc.2022.102250. PMID:35835220^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.