6ZCO

Crystal Structure of C-terminal Dimerization Domain of Nucleocapsid Phosphoprotein from SARS-CoV-2, crystal form II

Summary for 6ZCO

• Entry DOI: 10.2210/pdb6zco/pdb
• Descriptor: Nucleoprotein (2 entities in total)
• Functional Keywords: nucleoprotein, sars coronavirus 2, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV)
• Total number of polymer chains: 1
• Total formula weight: 15122.77

Authors

Zinzula, L.,Basquin, J.,Nagy, I.,Bracher, A. (deposition date: 2020-06-11, release date: 2020-07-01, Last modification date: 2024-01-24)

Primary citation

Zinzula, L.,Basquin, J.,Bohn, S.,Beck, F.,Klumpe, S.,Pfeifer, G.,Nagy, I.,Bracher, A.,Hartl, F.U.,Baumeister, W.
High-resolution structure and biophysical characterization of the nucleocapsid phosphoprotein dimerization domain from the Covid-19 severe acute respiratory syndrome coronavirus 2.
Biochem.Biophys.Res.Commun., 538:54-62, 2021

PubMed Abstract: Unprecedented by number of casualties and socio-economic burden occurring worldwide, the coronavirus disease 2019 (Covid-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the worst health crisis of this century. In order to develop adequate countermeasures against Covid-19, identification and structural characterization of suitable antiviral targets within the SARS-CoV-2 protein repertoire is urgently needed. The nucleocapsid phosphoprotein (N) is a multifunctional and highly immunogenic determinant of virulence and pathogenicity, whose main functions consist in oligomerizing and packaging the single-stranded RNA (ssRNA) viral genome. Here we report the structural and biophysical characterization of the SARS-CoV-2 N C-terminal domain (CTD), on which both N homo-oligomerization and ssRNA binding depend. Crystal structures solved at 1.44 Å and 1.36 Å resolution describe a rhombus-shape N CTD dimer, which stably exists in solution as validated by size-exclusion chromatography coupled to multi-angle light scattering and analytical ultracentrifugation. Differential scanning fluorimetry revealed moderate thermal stability and a tendency towards conformational change. Microscale thermophoresis demonstrated binding to a 7-bp SARS-CoV-2 genomic ssRNA fragment at micromolar affinity. Furthermore, a low-resolution preliminary model of the full-length SARS-CoV N in complex with ssRNA, obtained by cryo-electron microscopy, provides an initial understanding of self-associating and RNA binding functions exerted by the SARS-CoV-2 N.

PubMed: 33039147
DOI: 10.1016/j.bbrc.2020.09.131

Experimental method

X-RAY DIFFRACTION (1.361 Å)