9UJ2
14-3-3 zeta chimera with the S202R peptide of SARS-CoV-2 N (residues 200-213)
Summary for 9UJ2
| Entry DOI | 10.2210/pdb9uj2/pdb |
| Descriptor | 14-3-3 protein zeta/delta,Peptide from Nucleoprotein, 1,2-ETHANEDIOL, DI(HYDROXYETHYL)ETHER, ... (5 entities in total) |
| Functional Keywords | phosphopeptide, coronavirus, chimera, signaling protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 57478.54 |
| Authors | Boyko, K.M.,Matyuta, I.O.,Minyaev, M.E.,Perfilova, K.V.,Sluchanko, N.N. (deposition date: 2025-04-16, release date: 2025-05-21) |
| Primary citation | Perfilova, K.V.,Matyuta, I.O.,Minyaev, M.E.,Boyko, K.M.,Cooley, R.B.,Sluchanko, N.N. High-resolution structure reveals enhanced 14-3-3 binding by a mutant SARS-CoV-2 nucleoprotein variant with improved replicative fitness. Biochem.Biophys.Res.Commun., 767:151915-151915, 2025 Cited by PubMed Abstract: Replication of many viruses depends on phosphorylation of viral proteins by host protein kinases and subsequent recruitment of host protein partners. The nucleoprotein (N) of SARS-CoV-2 is heavily phosphorylated and recruits human phosphopeptide-binding 14-3-3 proteins early in infection, which is reversed prior to nucleocapsid assembly in new virions. Among the multiple phosphosites of N, which are particularly dense in the serine/arginine-rich interdomain region, phospho-Thr205 is highly relevant for 14-3-3 recruitment by SARS-CoV-2 N. The context of this site is mutated in most SARS-CoV-2 variants of concern. Among mutations that increase infectious virus titers, the S202R mutation (B.1.526 Iota) causes a striking replication boost (∼166-fold), although its molecular consequences have remained unclear. Here, we show that the S202R-mutated N phosphopeptide exhibits a 5-fold higher affinity for human 14-3-3ζ than the Wuhan variant and we rationalize this effect by solving a high-resolution crystal structure of the complex. The structure revealed an enhanced 14-3-3/N interface contributed by the Arg202 side chain that, in contrast to Ser202, formed multiple stabilizing contacts with 14-3-3, including water-mediated H-bonds and guanidinium pi-pi stacking. These findings provide a compelling link between the replicative fitness of SARS-CoV-2 and the N protein's affinity for host 14-3-3 proteins. PubMed: 40318379DOI: 10.1016/j.bbrc.2025.151915 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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