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. Description Intrinsically disordered SARS-CoV-2 nucleoprotein folds around its viral partner nsp3a to form a dynamic and compact complex.
【초록키워드】 COVID-19, SARS-CoV-2, Transcription, RNA, target, Nsp3, molecular, binding, association, Interaction, regulate, cofactor, replication-transcription complex, Factor, complex, domain, hydrophobic, description, genome replication, SARS-CoV-2 nucleoprotein, motif, chaperone, dimension, linker, atomic resolution, linear, provide, RTC, dimeric, engage, intrinsically, polar, bipartite, 【제목키워드】 complex, SARS-CoV-2 nucleoprotein, intrinsically,