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Open AccessArticle
Molecular Bases and Specificity behind the Activation of the Immune System OAS/RNAse L Pathway by Viral RNA
by
Emma Jung-Rodriguez
Emma Jung-Rodriguez 1,
Florent Barbault
Florent Barbault 1,
Emmanuelle Bignon
Emmanuelle Bignon 2
and
Antonio Monari
Antonio Monari 1,*
1
Université Paris Cité and CNR, ITODYS, F-75006 Paris, France
2
Université de Lorraine and CNRS, LPCT UMR 7019, F-54000 Nancy, France
*
Author to whom correspondence should be addressed.
Viruses 2024, 16(8), 1246; https://doi.org/10.3390/v16081246 (registering DOI)
Submission received: 8 July 2024
/
Revised: 31 July 2024
/
Accepted: 1 August 2024
/
Published: 2 August 2024
Abstract
The first line of defense against invading pathogens usually relies on innate immune systems. In this context, the recognition of exogenous RNA structures is primordial to fight, notably, against RNA viruses. One of the most efficient immune response pathways is based on the sensing of RNA double helical motifs by the oligoadenylate synthase (OAS) proteins, which in turn triggers the activity of RNase L and, thus, cleaves cellular and viral RNA. In this contribution, by using long-range molecular dynamics simulations, complemented with enhanced sampling techniques, we elucidate the structural features leading to the activation of OAS by interaction with a model double-strand RNA oligomer mimicking a viral RNA. We characterize the allosteric regulation induced by the nucleic acid leading to the population of the active form of the protein. Furthermore, we also identify the free energy profile connected to the active vs. inactive conformational transitions in the presence and absence of RNA. Finally, the role of two RNA mutations, identified as able to downregulate OAS activation, in shaping the protein/nucleic acid interface and the conformational landscape of OAS is also analyzed.
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MDPI and ACS Style
Jung-Rodriguez, E.; Barbault, F.; Bignon, E.; Monari, A.
Molecular Bases and Specificity behind the Activation of the Immune System OAS/RNAse L Pathway by Viral RNA. Viruses 2024, 16, 1246.
https://doi.org/10.3390/v16081246
AMA Style
Jung-Rodriguez E, Barbault F, Bignon E, Monari A.
Molecular Bases and Specificity behind the Activation of the Immune System OAS/RNAse L Pathway by Viral RNA. Viruses. 2024; 16(8):1246.
https://doi.org/10.3390/v16081246
Chicago/Turabian Style
Jung-Rodriguez, Emma, Florent Barbault, Emmanuelle Bignon, and Antonio Monari.
2024. "Molecular Bases and Specificity behind the Activation of the Immune System OAS/RNAse L Pathway by Viral RNA" Viruses 16, no. 8: 1246.
https://doi.org/10.3390/v16081246
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