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

  • 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.
Author:F. Cantini, L. Banci, Nadide AltincekicORCiDGND, Jasleen Kaur BainsORCiDGND, Karthikeyan DhamotharanORCiDGND, Christin FuksGND, Boris FürtigORCiDGND, S. L. Gande, Bruno Hargittay, Martin HengesbachORCiDGND, Marie Hutchison, Sophie M. KornORCiDGND, Nina Kubatova, Felicitas Kutz, Verena LinhardORCiD, Frank LöhrORCiD, Nathalie Meiser, Dennis Joshua Pyper, Nusrat QureshiORCiDGND, Christian RichterORCiDGND, Krishna SaxenaORCiDGND, Andreas SchlundtORCiDGND, Harald SchwalbeORCiDGND, Sridhar SreeramuluORCiDGND, Jan-Niklas TantsORCiD, Anna WackerORCiDGND, Julia E. WeigandORCiDGND, Jens WöhnertORCiDGND, A. C. Tsika, N. K. Fourkiotis, G. A. Spyroulias
Parent Title (English):Biomolecular NMR assignments
Publisher:Springer Netherlands
Place of publication:Dordrecht [u.a.]
Document Type:Article
Date of Publication (online):2020/08/14
Date of first Publication:2020/08/14
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/06/02
Tag:COVID19-NMR; Macrodomain; Non-structural protein; Protein drugability; SARS-CoV-2; Solution NMR-spectroscopy
Page Number:8
First Page:339
Last Page:346
Open Access funding provided by Projekt DEAL. Work at BMRZ is supported by the state of Hesse. Work in COVID19-NMR was supported by the Goethe Corona Funds and the DFG in CRC902: “Molecular Principles of RNA-based regulation.” Work at CERM is supported by the Italian Ministry for University and Research (FOE funding) to the Italian Center (CERM, University of Florence) of Instruct-ERIC, an European Research Infrastructure, ESFRI Landmark. The work was supported by the INSPIRED (MIS 5002550) which is implemented under the Action ‘Reinforcement of the Research and Innovation Infrastructure,’ funded by the Operational Program ‘Competitiveness, Entrepreneurship and Innovation’ (NSRF 2014–2020) and co-financed by Greece and the European Union (European Regional Development Fund).
Institutes:Biochemie, Chemie und Pharmazie
Wissenschaftliche Zentren und koordinierte Programme / Zentrum für Biomolekulare Magnetische Resonanz (BMRZ)
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften
5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Licence (German):License LogoCreative Commons - Namensnennung 4.0