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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. and Banci, L. and Altincekic, N. and Bains, J. K. and Dhamotharan, K. and Fuks, C. and Fürtig, B. and Gande, S. L. and Hargittay, B. and Hengesbach, M. and Hutchison, M. T. and Korn, S. M. and Kubatova, N. and Kutz, F. and Linhard, V. and Löhr, F. and Meiser, N. and Pyper, D. J. and Qureshi, N. S. and Richter, C. and Saxena, K. and Schlundt, A. and Schwalbe, H. and Sreeramulu, S. and Tants, J.-N. and Wacker, A. and Weigand, Julia E. and Wöhnert, J. and Tsika, A. C. and Fourkiotis, N. K. and 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), pp. 339-346. Springer, ISSN 1874-270X,
DOI: 10.1007/s12104-020-09973-4,
[Article]

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. and Banci, L. and Altincekic, N. and Bains, J. K. and Dhamotharan, K. and Fuks, C. and Fürtig, B. and Gande, S. L. and Hargittay, B. and Hengesbach, M. and Hutchison, M. T. and Korn, S. M. and Kubatova, N. and Kutz, F. and Linhard, V. and Löhr, F. and Meiser, N. and Pyper, D. J. and Qureshi, N. S. and Richter, C. and Saxena, K. and Schlundt, A. and Schwalbe, H. and Sreeramulu, S. and Tants, J.-N. and Wacker, A. and Weigand, Julia E. and Wöhnert, J. and Tsika, A. C. and Fourkiotis, N. K. and Spyroulias, G. A.
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
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.

Journal or Publication Title: Biomolecular NMR assignments
Journal volume: 14
Number: 2
Publisher: Springer
Divisions: 10 Department of Biology
10 Department of Biology > RNA Biochemistry
Date Deposited: 05 Mar 2021 08:28
DOI: 10.1007/s12104-020-09973-4
Official URL: https://link.springer.com/article/10.1007/s12104-020-09973-4...
Identification Number: pmid:32803496
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