The SARS-CoV-2 genome encodes for approximately 30 proteins. Within the international project COVID19-NMR, we distribute the spectroscopic analysis of the viral proteins and RNA. Here, we report NMR chemical shift assignments for the protein Nsp3b, a domain of Nsp3. The 217-kDa large Nsp3 protein contains multiple structurally independent, yet functionally related domains including the viral papain-like protease and Nsp3b, a macrodomain (MD). In general, the MDs of SARS-CoV and MERS-CoV were suggested to play a key role in viral replication by modulating the immune response of the host. The MDs are structurally conserved. They most likely remove ADP-ribose, a common posttranslational modification, from protein side chains. This de-ADP ribosylating function has potentially evolved to protect the virus from the anti-viral ADP-ribosylation catalyzed by poly-ADP-ribose polymerases (PARPs), which in turn are triggered by pathogen-associated sensing of the host immune system. This renders the SARS-CoV-2 Nsp3b a highly relevant drug target in the viral replication process. We here report the near-complete NMR backbone resonance assignment (1H, 13C, 15N) of the putative Nsp3b MD in its apo form and in complex with ADP-ribose. Furthermore, we derive the secondary structure of Nsp3b in solution. In addition, 15N-relaxation data suggest an ordered, rigid core of the MD structure. These data will provide a basis for NMR investigations targeted at obtaining small-molecule inhibitors interfering with the catalytic activity of Nsp3b.

1H, 13C, and 15N backbone chemical shift assignments of the apo and the ADP-ribose bound forms of the macrodomain of SARS-CoV-2 non-structural protein 3b / Cantini F.; Banci L.; Altincekic N.; Bains J.K.; Dhamotharan K.; Fuks C.; Furtig B.; Gande S.L.; Hargittay B.; Hengesbach M.; Hutchison M.T.; Korn S.M.; Kubatova N.; Kutz F.; Linhard V.; Lohr F.; Meiser N.; Pyper D.J.; Qureshi N.S.; Richter C.; Saxena K.; Schlundt A.; Schwalbe H.; Sreeramulu S.; Tants J.-N.; Wacker A.; Weigand J.E.; Wohnert J.; Tsika A.C.; Fourkiotis N.K.; Spyroulias G.A.. - In: BIOMOLECULAR NMR ASSIGNMENTS. - ISSN 1874-2718. - STAMPA. - 14(2020), pp. 339-346. [10.1007/s12104-020-09973-4]

1H, 13C, and 15N backbone chemical shift assignments of the apo and the ADP-ribose bound forms of the macrodomain of SARS-CoV-2 non-structural protein 3b

Cantini F.;Banci L.
;
2020

Abstract

The SARS-CoV-2 genome encodes for approximately 30 proteins. Within the international project COVID19-NMR, we distribute the spectroscopic analysis of the viral proteins and RNA. Here, we report NMR chemical shift assignments for the protein Nsp3b, a domain of Nsp3. The 217-kDa large Nsp3 protein contains multiple structurally independent, yet functionally related domains including the viral papain-like protease and Nsp3b, a macrodomain (MD). In general, the MDs of SARS-CoV and MERS-CoV were suggested to play a key role in viral replication by modulating the immune response of the host. The MDs are structurally conserved. They most likely remove ADP-ribose, a common posttranslational modification, from protein side chains. This de-ADP ribosylating function has potentially evolved to protect the virus from the anti-viral ADP-ribosylation catalyzed by poly-ADP-ribose polymerases (PARPs), which in turn are triggered by pathogen-associated sensing of the host immune system. This renders the SARS-CoV-2 Nsp3b a highly relevant drug target in the viral replication process. We here report the near-complete NMR backbone resonance assignment (1H, 13C, 15N) of the putative Nsp3b MD in its apo form and in complex with ADP-ribose. Furthermore, we derive the secondary structure of Nsp3b in solution. In addition, 15N-relaxation data suggest an ordered, rigid core of the MD structure. These data will provide a basis for NMR investigations targeted at obtaining small-molecule inhibitors interfering with the catalytic activity of Nsp3b.
14
339
346
Goal 3: Good health and well-being
Cantini F.; Banci L.; Altincekic N.; Bains J.K.; Dhamotharan K.; Fuks C.; Furtig B.; Gande S.L.; Hargittay B.; Hengesbach M.; Hutchison M.T.; Korn S.M.; Kubatova N.; Kutz F.; Linhard V.; Lohr F.; Meiser N.; Pyper D.J.; Qureshi N.S.; Richter C.; Saxena K.; Schlundt A.; Schwalbe H.; Sreeramulu S.; Tants J.-N.; Wacker A.; Weigand J.E.; Wohnert J.; Tsika A.C.; Fourkiotis N.K.; Spyroulias G.A.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2158/1211622
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