Coronavirus nucleocapsid protein

Source: Wikipedia, the free encyclopedia.
Nucleocapsid protein
virion.[1] The N protein, contained entirely within the virion, is not visible.
Blue: envelope
Turquoise: spike glycoprotein (S)
Red: envelope proteins (E)
Green: membrane proteins (M)
Orange: glycans
Identifiers
SymbolCoV_nucleocap
PfamPF00937
InterProIPR001218
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

The nucleocapsid (N) protein is a

antibodies to N are found in patients recovered from SARS and COVID-19.[5]

History

COVID-19 was first identified in January 2020. A patient in the state of Washington was given a diagnosis of coronavirus infection on 20 January. A group of scientists based at the

genomic sequence, replication properties and cell culture tropism from the swabs. They made available the virus to the wider scientific community shortly thereafter "by depositing it into two virus reagent repositories".[6]

Structure

X-ray crystallography structure of the dimer formed by two C-terminal domains from the SARS-CoV-2 N protein.[7]

The N protein is composed of two main

amino acid residues long[2] and in SARS-CoV-2, the causative agent of COVID-19, it is 419 residues long.[7][8]

Both the

conserved sequence motif rich in serine and arginine residues (the SR-rich region), may also be implicated in dimer formation, though reports on this vary.[2][3] Although higher-order oligomers formed through the C-terminal domain have been observed crystallographically, it is unclear if these structures have a physiological role.[2][9]

The C-terminal dimer has been structurally characterized by

Post-translational modifications

The N protein is post-translationally modified by phosphorylation at sites located in the IDR, particularly in the SR-rich region.[2][11] SARS-CoV-2 nucleocapsid (N) protein is arginine methylated by protein arginine methyltransferase 1 (PRMT1) at residues R95 and R177. Type I PRMT inhibitor (MS023) or substitution of R95 or R177 with lysine inhibited interaction of N protein with the 5’-UTR of SARS-CoV-2 genomic RNA, a property required for viral packaging | doi: 10.1016/j.jbc.2021.100821 | PMID 34029587. In several coronaviruses,

SUMOylated and the N proteins of several coronaviruses including SARS-CoV-2 have been observed to be proteolytically cleaved.[11][13][14]

Expression and localization

The N protein is the most highly

N protein is localized primarily to the cytoplasm.[3] In many coronaviruses, a population of N protein is localized to the nucleolus,[3][4][15] thought to be associated with its effects on the cell cycle.[4]

Function

Genome packaging and viral assembly

respiratory mucosa, showing the positions of the four structural proteins and components of the extracellular environment.[16]
NMR structure of the SARS-CoV-2 N protein N-terminal domain (red) in complex with double-stranded RNA (orange and yellow).[10]

The N protein binds to

RNA structure in the genomic RNA.[3][9]

Genomic and subgenomic RNA synthesis

Synthesis of genomic RNA appears to involve participation by the N protein. N is physically colocalized with the viral RNA-dependent RNA polymerase early in the replication cycle and forms interactions with non-structural protein 3, a component of the replicase-transcriptase complex.[3] Although N appears to facilitate efficient replication of genomic RNA, it is not required for RNA transcription in all coronaviruses.[3][17] In at least one coronavirus, transmissible gastroenteritis virus (TGEV), N is involved in template switching in the production of subgenomic mRNAs, a process that is a distinctive feature of viruses in the order Nidovirales.[3][17][18]

Cell cycle effects

Coronaviruses manipulate the

protein translation activity.[3]

Immune system effects

The N protein is involved in

MERS-CoV,[21] and SARS-CoV-2,[22] N has been reported as suppressing interferon
responses.

Evolution and conservation

The sequences and structures of N proteins from different coronaviruses, particularly the C-terminal domains, appear to be well conserved.

arteriviruses suggest a common evolutionary origin and supports the classification of these two groups in the common order Nidovirales.[2][3]

Examination of SARS-CoV-2 sequences collected during the

The N protein's properties of being well conserved, not appearing to recombine frequently, and producing a strong T-cell response have led to it being studied as a potential target for coronavirus vaccines.[25][26][23][27] The vaccine candidate UB-612 is one such experimental vaccine that targets the N protein, along with other viral proteins, to attempt to induce broad immunity.[28][29]

References

  1. ^ Solodovnikov, Alexey; Arkhipova, Valeria (2021-07-29). "Достоверно красиво: как мы сделали 3D-модель SARS-CoV-2" [Truly beautiful: how we made the SARS-CoV-2 3D model] (in Russian). N+1. Archived from the original on 2021-07-30. Retrieved 30 July 2021.
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