7QIP

SARS-CoV-2 Nucleocapsid phosphopeptide 201-210 bound to human 14-3-3 sigma

Summary for 7QIP

• Entry DOI: 10.2210/pdb7qip/pdb
• Descriptor: 14-3-3 protein sigma, ARG-GLY-TPO-SER-PRO-ALA-ARG-MET, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: phosphopeptide-binding, universal regulatory hub, protein-peptide complex, coronavirus protein fragment, peptide binding protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 54883.75

Authors

Sluchanko, N.N.,Tugaeva, K.V.,Smith, J.L.R.,Antson, A.A. (deposition date: 2021-12-15, release date: 2021-12-29, Last modification date: 2025-01-08)

Primary citation

Tugaeva, K.V.,Sysoev, A.A.,Kapitonova, A.A.,Smith, J.L.R.,Zhu, P.,Cooley, R.B.,Antson, A.A.,Sluchanko, N.N.
Human 14-3-3 Proteins Site-selectively Bind the Mutational Hotspot Region of SARS-CoV-2 Nucleoprotein Modulating its Phosphoregulation.
J.Mol.Biol., 435:167891-167891, 2023

PubMed Abstract: Phosphorylation of SARS-CoV-2 nucleoprotein recruits human cytosolic 14-3-3 proteins playing a well-recognized role in replication of many viruses. Here we use genetic code expansion to demonstrate that 14-3-3 binding is triggered by phosphorylation of SARS-CoV-2 nucleoprotein at either of two pseudo-repeats centered at Ser197 and Thr205. According to fluorescence anisotropy measurements, the pT205-motif,presentin SARS-CoV-2 but not in SARS-CoV, is preferred over the pS197-motif by all seven human 14-3-3 isoforms, which collectively display an unforeseen pT205/pS197 peptide binding selectivity hierarchy. Crystal structures demonstrate that pS197 and pT205 are mutually exclusive 14-3-3-binding sites, whereas SAXS and biochemical data obtained on the full protein-protein complex indicate that 14-3-3 binding occludes the Ser/Arg-rich region of the nucleoprotein, inhibiting its dephosphorylation. This Ser/Arg-rich region is highly prone to mutations, as exemplified by the Omicron and Delta variants, with our data suggesting that the strength of 14-3-3/nucleoprotein interaction can be linked with the replicative fitness of the virus.

PubMed: 36427566
DOI: 10.1016/j.jmb.2022.167891

Experimental method

X-RAY DIFFRACTION (2.65 Å)