ArticleJournal of virology2006
Molecular determinants of substrate specificity for Semliki Forest virus nonstructural protease.
Article in Journal of virology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed.
- Chikungunya virus nsP2: Insights into viral replication, pathogenesis, and therapeutic targeting.Virulence · 2026Review
- Article
- Trans-complementation of chikungunya virus replicase mutants reveals alphavirus replication complexity and supports antiviral tool development.PLoS pathogens · 2025Article
- Alphavirus nsP2: A Multifunctional Regulator of Viral Replication and Promising Target for Anti-Alphavirus Therapies.Reviews in medical virology · 2025Review
- A robust fluorogenic substrate for chikungunya virus protease (nsP2) activity.Protein science : a publication of the Protein Society · 2025Article
- The Rac1-PAK1-Arp2/3 signaling axis regulates CHIKV nsP1-induced filopodia and optimal viral genome replication.Journal of virology · 2024Article
- Precursors of Viral Proteases as Distinct Drug Targets.Viruses · 2021Review
- Semliki Forest Virus Chimeras with Functional Replicase Modules from Related Alphaviruses Survive by Adaptive Mutations in Functionally Important Hot Spots.Journal of virology · 2021Article
- Alphavirus-Induced Membrane Rearrangements during Replication, Assembly, and Budding.Pathogens (Basel, Switzerland) · 2021Review
- Chikungunya and Zika Viruses: Co-Circulation and the Interplay between Viral Proteins and Host Factors.Pathogens (Basel, Switzerland) · 2021Review
- Article
- Specificity Studies of the Venezuelan Equine Encephalitis Virus Non-Structural Protein 2 Protease Using Recombinant Fluorescent Substrates.International journal of molecular sciences · 2020Article
- Sensitivity of Alphaviruses to G3BP Deletion Correlates with Efficiency of Replicase Polyprotein Processing.Journal of virology · 2020Article
- Timeliness of Proteolytic Events Is Prerequisite for Efficient Functioning of the Alphaviral Replicase.Journal of virology · 2018Article
- Mutation of CD2AP and SH3KBP1 Binding Motif in Alphavirus nsP3 Hypervariable Domain Results in Attenuated Virus.Viruses · 2018Article
- Review
- Design and Validation of Novel Chikungunya Virus Protease Inhibitors.Antimicrobial agents and chemotherapy · 2016Article
- Chikungunya virus infectivity, RNA replication and non-structural polyprotein processing depend on the nsP2 protease's active site cysteine residue.Scientific reports · 2016Article
- Chikungunya nsP2 protease is not a papain-like cysteine protease and the catalytic dyad cysteine is interchangeable with a proximal serine.Scientific reports · 2015Article
- Differences in Processing Determinants of Nonstructural Polyprotein and in the Sequence of Nonstructural Protein 3 Affect Neurovirulence of Semliki Forest Virus.Journal of virology · 2015Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
The C-terminal cysteine protease domain of Semliki Forest virus nonstructural protein 2 (nsP2) regulates the virus life cycle by sequentially cleaving at three specific sites within the virus-encoded replicase polyprotein P1234. The site between nsP3 and nsP4 (the 3/4 site) is cleaved most efficiently. Analysis of Semliki Forest virus-specific cleavage sites with shuffled N-terminal and C-terminal half-sites showed that the main determinants of cleavage efficiency are located in the region preceding the cleavage site. Random mutagenesis analysis revealed that amino acid residues in positions P4, P3, P2, and P1 of the 3/4 cleavage site cannot tolerate much variation, whereas in the P5 position most residues were permitted. When mutations affecting cleavage efficiency were introduced into the 2/3 and 3/4 cleavage sites, the resulting viruses remained viable but had similar defects in P1234 processing as observed in the in vitro assay. Complete blockage of the 3/4 cleavage was found to be lethal. The amino acid in position P1' had a significant effect on cleavage efficiency, and in this regard the protease markedly preferred a glycine residue over the tyrosine natively present in the 3/4 site. Therefore, the cleavage sites represent a compromise between protease recognition and other requirements of the virus life cycle. The protease recognizes at least residues P4 to P1', and the P4 arginine residue plays an important role in the fast cleavage of the 3/4 site.
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