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Macro1 domain residue F156: A hallmark of SARS-CoV-2 de-MARylation specificity.

Virology (2023-07-31)
Oney Ortega Granda, Karine Alvarez, Maria J Mate-Perez, Bruno Canard, François Ferron, Nadia Rabah
RESUMEN

SARS-CoV-2 is a large, enveloped and positive sense single stranded RNA virus. Its genome codes for 16 non-structural proteins. The largest protein of this complex is nsp3, that contains a well conserved Macro1 domain. Viral Macro domains were shown to bind to mono-ADP-ribose (MAR) and poly-ADP-ribose (PAR) in their free form or conjugated to protein substrates. They carry ADP-ribose hydrolase activities implicated in the regulation of innate immunity. SARS-CoV-2 and SARS-CoV show widely different induction and handling of the host interferon response. Herein, we have conducted a mutational study on the key amino-acid residue F156 in SARS-CoV-2, pinpointed by bioinformatic and structural studies, and its cognate residue N157 in SARS-CoV. Our data suggest that the exchange of these residues slightly modifies ADP-ribose binding, but drastically impacts de-MARylation activity. Alanine substitutions at this position hampers PAR binding, abolishes MAR hydrolysis of SARS-CoV-2, and reduces by 70% this activity in the case of SARS-CoV.

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Sigma-Aldrich
Reactivo de unión anti-poli-ADP-ribosa, Anti-poly-ADP-ribose binding reagent is a reagent that selectively binds to ADP ribose for use in Western Blotting, Immunocytochemistry and Dot Blot.
Sigma-Aldrich
Reactivo de unión anti-mono-ADP-ribosa, from Escherichia coli