6YUN

1.45 Angstrom Resolution Crystal Structure of C-terminal Dimerization Domain of Nucleocapsid Phosphoprotein from SARS-CoV-2


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.44 Å
  • R-Value Free: 0.189 
  • R-Value Work: 0.148 
  • R-Value Observed: 0.150 

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This is version 1.3 of the entry. See complete history


Literature

High-resolution structure and biophysical characterization of the nucleocapsid phosphoprotein dimerization domain from the Covid-19 severe acute respiratory syndrome coronavirus 2.

Zinzula, L.Basquin, J.Bohn, S.Beck, F.Klumpe, S.Pfeifer, G.Nagy, I.Bracher, A.Hartl, F.U.Baumeister, W.

(2021) Biochem Biophys Res Commun 538: 54-62

  • DOI: https://doi.org/10.1016/j.bbrc.2020.09.131
  • Primary Citation of Related Structures:  
    6YUN, 6ZCO

  • 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.


  • Organizational Affiliation

    The Max-Planck Institute of Biochemistry, Department of Molecular Structural Biology, Am Klopferspitz 18, 82152, Martinsried, Germany. Electronic address: zinzula@biochem.mpg.de.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Nucleoprotein
A, B
135Severe acute respiratory syndrome coronavirus 2Mutation(s): 0 
UniProt
Find proteins for P0DTC9 (Severe acute respiratory syndrome coronavirus 2)
Explore P0DTC9 
Go to UniProtKB:  P0DTC9
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0DTC9
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.44 Å
  • R-Value Free: 0.189 
  • R-Value Work: 0.148 
  • R-Value Observed: 0.150 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 43.43α = 90
b = 46.856β = 90
c = 131.947γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
Aimlessdata reduction
XDSdata scaling
PHASERphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2020-05-20
    Type: Initial release
  • Version 1.1: 2020-11-04
    Changes: Database references
  • Version 1.2: 2021-03-03
    Changes: Database references
  • Version 1.3: 2024-01-24
    Changes: Data collection, Database references, Refinement description