Abstract
The current outbreak of the highly infectious COVID-19 respiratory disease is caused by the novel coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). To fight the pandemic, the search for promising viral drug targets has become a cross-border common goal of the international biomedical research community. Within the international Covid19-NMR consortium, scientists support drug development against SARS-CoV-2 by providing publicly available NMR data on viral proteins and RNAs. The coronavirus nucleocapsid protein (N protein) is an RNA-binding protein involved in viral transcription and replication. Its primary function is the packaging of the viral RNA genome. The highly conserved architecture of the coronavirus N protein consists of an N-terminal RNA-binding domain (NTD), followed by an intrinsically disordered Serine/Arginine (SR)-rich linker and a C-terminal dimerization domain (CTD). Besides its involvement in oligomerization, the CTD of the N protein (N-CTD) is also able to bind to nucleic acids by itself, independent of the NTD. Here, we report the near-complete NMR backbone chemical shift assignments of the SARS-CoV-2 N-CTD to provide the basis for downstream applications, in particular site-resolved drug binding studies.
Highlights
SARS-CoV-2 is the newest representative of the coronavirus family transmissible to humans and the cause of the COVID-19 respiratory disease
The N protein mainly exists as a homodimer (Chang et al 2005; Zhou et al 2020), but based on the extended N-C-terminal dimerization domain (CTD) it tends to form less stable higher-oligomers (Ye et al 2020), such as octamers, as was suggested for SARS-CoV (Chen et al 2007)
The high degree of structural conservation of the CTD dimer is obvious from a structural comparison, e.g. of the SARS-CoV-2 PDB entry 7C22 (Zhou et al 2020) with the SARS-CoV homolog represented by PDB entry 2CJR (Chen et al 2007), yielding an RMSD of backbone atoms of 0.46 Å
Summary
This study uses the SARS-CoV-2 NCBI reference genome entry NC_045512.2, identical to GenBank entry MN90894 (Wu et al 2020). For the SARS-CoV-2 N-CTD we find a second, minor population for the backbone amides of residues Thr1-Ala and the very C-terminal stretch between Ala113 and Phe117 (Fig. 1). For the latter, we assume that this occurrence is due to the cis/trans equilibrium based on Pro118. The N-terminal amino acids 4-13 are present as an α-helix in some available crystal structures (here compared to PDB 7C22 (Zhou et al 2020)), and our analysis of SARSCoV-2 secondary chemical shifts (Fig. 2b) indicates this tendency in solution (see below), while we only find a fully structured protein backbone starting from residue 13. We calculated carbon secondary chemical shifts based on the chemical shifts of C α and Cβ (Fig. 2b)
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