7PKU

Structure of SARS-CoV-2 nucleoprotein in dynamic complex with its viral partner nsp3a

Summary for 7PKU

• Entry DOI: 10.2210/pdb7pku/pdb
• NMR Information: BMRB: 34661
• Descriptor: 3C-like proteinase, Nucleoprotein (2 entities in total)
• Functional Keywords: sars-cov-2; nucleoprotein; nsp3; nmr; intrinsically disordered protein; chaperone; replication; nucleocapsid; rna; saxs, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); More
• Total number of polymer chains: 2
• Total formula weight: 18603.83

Authors

Bessa, L.M.,Guseva, S.,Camacho-Zarco, A.R.,Salvi, N.,Blackledge, M. (deposition date: 2021-08-26, release date: 2022-01-19, Last modification date: 2024-06-19)

Primary citation

Bessa, L.M.,Guseva, S.,Camacho-Zarco, A.R.,Salvi, N.,Maurin, D.,Perez, L.M.,Botova, M.,Malki, A.,Nanao, M.,Jensen, M.R.,Ruigrok, R.W.H.,Blackledge, M.
The intrinsically disordered SARS-CoV-2 nucleoprotein in dynamic complex with its viral partner nsp3a.
Sci Adv, 8:eabm4034-eabm4034, 2022

PubMed Abstract: 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 (LALLLLDRLNQL) and a disordered polar strand (GQTVTKKSAAEAS), 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.

PubMed: 35044811
DOI: 10.1126/sciadv.abm4034

Experimental method

SOLUTION NMR