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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. ; Fürtig, B. ; Gande, S. L. ; Hargittay, B. ; Hengesbach, M. ; Hutchison, M. T. ; Korn, S. M. ; Kubatova, N. ; Kutz, F. ; Linhard, V. ; Löhr, 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, Julia E. ; Wöhnert, J. ; Tsika, A. C. ; Fourkiotis, N. K. ; Spyroulias, G. A. (2020)
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.
In: Biomolecular NMR assignments, 14 (2)
doi: 10.1007/s12104-020-09973-4
Article, Bibliographie

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 (H, C, N) 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, N-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.

Item Type: Article
Erschienen: 2020
Creators: Cantini, F. ; Banci, L. ; Altincekic, N. ; Bains, J. K. ; Dhamotharan, K. ; Fuks, C. ; Fürtig, B. ; Gande, S. L. ; Hargittay, B. ; Hengesbach, M. ; Hutchison, M. T. ; Korn, S. M. ; Kubatova, N. ; Kutz, F. ; Linhard, V. ; Löhr, 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, Julia E. ; Wöhnert, J. ; Tsika, A. C. ; Fourkiotis, N. K. ; Spyroulias, G. A.
Type of entry: Bibliographie
Title: 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
Language: English
Date: 14 August 2020
Publisher: Springer
Journal or Publication Title: Biomolecular NMR assignments
Volume of the journal: 14
Issue Number: 2
DOI: 10.1007/s12104-020-09973-4
URL / URN: https://link.springer.com/article/10.1007/s12104-020-09973-4...
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 (H, C, N) 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, N-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.

Identification Number: pmid:32803496
Divisions: 10 Department of Biology
10 Department of Biology > RNA Biochemistry
Date Deposited: 05 Mar 2021 08:28
Last Modified: 05 Mar 2021 08:28
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