Disease relevance of N

• In the present study, we prove that the N protein of SARS-CoV can inhibit S phase progression in mammalian cell lines [1].
• N protein expression was found to directly inhibit the activity of the cyclin-CDK complex, resulting in hypophosphorylation of retinoblastoma protein with a concomitant down-regulation in E2F1-mediated transactivation [1].
• It is noted, however, that the N protein of SARS-CoV (SARS-CoV N) shares little homology with nucleocapsid proteins of other members of the coronavirus family [Science 300 (2003) 1399; Science 300 (2003) 1394] [2].
• Finally, the full-length nucleocapsid protein expressed and purified from baculovirus system was found to form different levels of higher order structures as detected by Western blot analysis of the fractionated proteins [2].
• The subcellular localization of severe acute respiratory syndrome coronavirus (SARS-CoV) N protein was studied [3].

High impact information on N

• These data suggest that the S phase inhibitory activity of the N protein may have major significance during viral pathogenesis [1].
• Analysis of RXL and CDK phosphorylation mutant N protein identified the mechanism of inhibition of CDK4 and CDK2 activity to be different [1].
• In many coronaviruses, the nucleocapsid protein (N protein) has been shown to inhibit cell cycle progression although the mechanism behind this is poorly understood [1].
• The nucleocapsid (N) protein plays an essential role in SARS-CoV genome packaging and virion assembly [4].
• Crystal structure of the severe acute respiratory syndrome (SARS) coronavirus nucleocapsid protein dimerization domain reveals evolutionary linkage between corona- and arteriviridae [4].

Biological context of N

• The genome of SARS Coronavirus (SARS-CoV) has recently been sequenced, and a number of genes identified, including that of the nucleocapsid protein (N) [2].
• The dimerization domain of N was mapped through studies of the oligomeric states of several truncated mutants [5].
• The coronavirus nucleocapsid (N) protein is a viral RNA-binding protein with multiple functions in terms of virus replication and modulating cell signalling pathways [3].
• This was found to be a novel nucleocapsid protein that matched almost exactly one predicted by an open reading frame in the recently published nucleotide sequence of the same virus isolate (>96% coverage) [6].
• The SARS coronavirus nucleocapsid protein induces actin reorganization and apoptosis in COS-1 cells in the absence of growth factors [7].

Anatomical context of N

• Group 1 antibodies recognized epitopes located slightly differently in N from those of group 2 antibodies, and a mouse hybridoma antibody resembling the former type was generated [8].
• However, only seven of these (group 1) had sera which also reacted with the native N antigen expressed in SARS-CoV-infected Vero cells, N-transfected 293T cells, and tissues of infected SARS patients [8].
• The N-specific IFN-gamma(+)CD4(+) T cells were mainly composed of CD45RA(-)CCR7(+)CD62L(-) cells, whereas IFN-gamma(+)CD8(+) memory T cells were mostly contained within CD45RA(+)CCR7(-)CD62L(-) cell population [9].
• This region spanning amino acids 249-395 contains predominant B cell epitopes located at the C-terminus of N protein [10].
• The full length NP could be expressed in E. coli at very high level within inclusion bodies [11].

Associations of N with chemical compounds

• Furthermore, deletion of leucine rich region (220-LALLLLDRLNRL) resulted in the accumulation of N to the cytoplasm and nucleolus, and when fusing this peptide to EGFP localization was cytoplasmic, suggesting that the N may act as a shuttle protein [12].
• In contrast, mutation of amino acid Gln-74 to an alanine, which does not affect the binding activity of the N-terminal domain, showed minimal, if any, detrimental effect on the infectivity of IBV [13].

Analytical, diagnostic and therapeutic context of N

• To determine the role of these putative NLSs in the intracellular localization of the SARS-CoV N, we performed a confocal microscopy analysis using rabbit anti-N antisera [12].
• Based on its 3D structure, we used site-directed mutagenesis to identify residues essential for the RNA-binding activity of the IBV N protein and viral infectivity [13].
• The use of recombinant severe acute respiratory syndrome-coronavirus (SARS-CoV) nucleocapsid protein (N) enzyme-linked immunosorbent assay (ELISA)-based antibody and antigen tests for diagnosis of SARS-CoV infections have been widely reported [14].
• Detection of specific antibodies to severe acute respiratory syndrome (SARS) coronavirus nucleocapsid protein for serodiagnosis of SARS coronavirus pneumonia [15].
• In this work, by using yeast two-hybrid and surface plasmon resonance techniques, the residues 197-221 of the membrane protein and the residues 351-422 of the nucleocapsid protein were determined to be involved in their interaction [16].

References