RdRP binds hRSV nucleocapsid

Stable Identifier
R-HSA-9833933
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Human respiratory syncytial virus A
Compartment
cytosol
ReviewStatus
5/5
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RdRP binds hRSV nucleocapsid
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Binding of P protein to N protein enables loading of the RNA-driven RNA polymerase (RdRP) complex to the ribonucleocapsid of the respiratory syncytial virus (RSV). The RdRP complex consists of P protein (cofactor) and L protein (catalytic subunit). M2-1 protein, which acts as a processivity factor, is also associated with the RdRP complex. While some studies describe M2-1 as a constitutive subunit of the RdRP complex, other studies consider it to be an accessory subunit as the replication can proceed without it, albeit with reduced efficacy (reviewed in Fearns and Deval 2016). Residues 172-176 of the P protein, as well as the adjacent charged residues play an important role in the interaction with the N protein and efficient viral replication and transcription (Lu et al. 2002). The nine C-terminal amino acids of P protein may be sufficient for binding to the ribonucleocapsid (Tran et al. 2007; Shapiro et al. 2014). In particular, the C-terminal phenylalanine (F241) of P protein was shown to play an important role in anchoring P protein to N protein (Khodjoyan et al. 2022). Based on RNA-free assays, the N-terminus of P protein may also contribute to its binding to the N protein (Galloux et al. 2015). A hydrophobic pocket in the N-terminal core domain of the N protein acts as a P protein binding domain (Galloux et al. 2012). Viral proteins N, L, P, and M2-1, and the genomic RSV RNA form the RNA synthesis ribonucleoprotein (RNP) complex (reviewed by Cao et al. 2021). This complex serves as a template for RNA replication, generating the (+) RNA antigenome and the (-) RNA genome, as well as for RNA transcription, producing capped and polyadenylated mRNAs.
Literature References
PubMed ID Title Journal Year
25568210 Identification and characterization of the binding site of the respiratory syncytial virus phosphoprotein to RNA-free nucleoprotein

Galloux, M, Gabiane, G, Sourimant, J, Richard, CA, England, P, Moudjou, M, Aumont-Nicaise, M, Fix, J, Rameix-Welti, MA, Eléouët, JF

J Virol 2015
22623798 Characterization of a viral phosphoprotein binding site on the surface of the respiratory syncytial nucleoprotein

Galloux, M, Tarus, B, Blazevic, I, Fix, J, Duquerroy, S, Eléouët, JF

J Virol 2012
27575793 New antiviral approaches for respiratory syncytial virus and other mononegaviruses: Inhibiting the RNA polymerase

Fearns, R, Deval, J

Antiviral Res 2016
34063087 Structural Insights into the Respiratory Syncytial Virus RNA Synthesis Complexes

Cao, D, Gao, Y, Liang, B

Viruses 2021
36614009 Investigation of the Fuzzy Complex between RSV Nucleoprotein and Phosphoprotein to Optimize an Inhibition Assay by Fluorescence Polarization

Khodjoyan, S, Morissette, D, Hontonnou, F, Checa Ruano, L, Richard, CA, Sperandio, O, Eléouët, JF, Galloux, M, Durand, P, Deville-Foillard, S, Sizun, C

Int J Mol Sci 2022
31953395 Cryo-EM structure of the respiratory syncytial virus RNA polymerase

Cao, D, Gao, Y, Roesler, C, Rice, S, D'Cunha, P, Zhuang, L, Slack, J, Domke, M, Antonova, A, Romanelli, S, Keating, S, Forero, G, Juneja, P, Liang, B

Nat Commun 2020
11861854 Identification of temperature-sensitive mutations in the phosphoprotein of respiratory syncytial virus that are likely involved in its interaction with the nucleoprotein

Lu, B, Brazas, R, Ma, CH, Kristoff, T, Cheng, X, Jin, H

J Virol 2002
17170452 The nine C-terminal amino acids of the respiratory syncytial virus protein P are necessary and sufficient for binding to ribonucleoprotein complexes in which six ribonucleotides are contacted per N protein protomer

Tran, TL, Castagné, N, Bhella, D, Varela, PF, Bernard, J, Chilmonczyk, S, Berkenkamp, S, Benhamo, V, Grznarova, K, Grosclaude, J, Nespoulos, C, Rey, FA, Eléouët, JF

J Gen Virol 2007
25407889 Quantitative investigation of the affinity of human respiratory syncytial virus phosphoprotein C-terminus binding to nucleocapsid protein

Shapiro, AB, Gao, N, O'Connell, N, Hu, J, Thresher, J, Gu, RF, Overman, R, Hardern, IM, Sproat, GG

Virol J 2014
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Authored
Orlic-Milacic, M  (2023-05-04)
Reviewed
Bergeron, HC  (2023-11-03)
Created
Orlic-Milacic, M  (2023-05-04)
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