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Article Dans Une Revue Science Advances Année : 2022

The intrinsically disordered SARS-CoV-2 nucleoprotein in dynamic complex with its viral partner nsp3a

Résumé

The processes of genome replication and transcription of SARS-CoV-2 represent important targets for viral inhibition. Betacoronaviral nucleoprotein (N) is a highly dynamic cofactor of the replication-transcription complex (RTC), whose function depends on an essential interaction with the amino-terminal ubiquitin-like domain of nsp3 (Ubl1). Here, we describe this complex (dissociation constant - 30 to 200 nM) at atomic resolution. The interaction implicates two linear motifs in the intrinsically disordered linker domain (N3), a hydrophobic helix ((219)LALLLLDRLNQL(230)) and a disordered polar strand ((243)GQTVTKKSAAEAS(255)), that mutually engage to form a bipartite interaction, folding N3 around Ubl1. This results in substantial collapse in the dimensions of dimeric N, forming a highly compact molecular chaperone, that regulates binding to RNA, suggesting a key role of nsp3 in the association of N to the RTC. The identification of distinct linear motifs that mediate an important interaction between essential viral factors provides future targets for development of innovative strategies against COVID-19.
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Dates et versions

hal-03621049 , version 1 (13-07-2022)

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Luiza Mamigonian Bessa, Serafima Guseva, Aldo Camacho-Zarco, Nicola Salvi, Damien Maurin, et al.. The intrinsically disordered SARS-CoV-2 nucleoprotein in dynamic complex with its viral partner nsp3a. Science Advances , 2022, 8 (3), pp.eabm4034-1-eabm4034-12. ⟨10.1126/sciadv.abm4034⟩. ⟨hal-03621049⟩
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