Open Access
Journal of Molecular Biology, volume 435, issue 2, pages 167891
Human 14-3-3 Proteins Site-selectively Bind the Mutational Hotspot Region of SARS-CoV-2 Nucleoprotein Modulating its Phosphoregulation
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2
York Structural Biology Laboratory, Department of Chemistry, University of York, York YO10 5DD, United Kingdom
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3
Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA
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Publication type: Journal Article
Publication date: 2023-01-01
Journal:
Journal of Molecular Biology
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 5.6
ISSN: 00222836, 10898638
PubMed ID:
36427566
Molecular Biology
Structural Biology
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.
Citations by journals
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ACS Central Science
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ACS Central Science
1 publication, 16.67%
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Protein Science
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Protein Science
1 publication, 16.67%
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mBio
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mBio
1 publication, 16.67%
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1
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Citations by publishers
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1
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American Chemical Society (ACS)
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American Chemical Society (ACS)
1 publication, 16.67%
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Wiley
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Wiley
1 publication, 16.67%
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American Society for Microbiology
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American Society for Microbiology
1 publication, 16.67%
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1
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- We do not take into account publications that without a DOI.
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Tugaeva K. V. et al. Human 14-3-3 Proteins Site-selectively Bind the Mutational Hotspot Region of SARS-CoV-2 Nucleoprotein Modulating its Phosphoregulation // Journal of Molecular Biology. 2023. Vol. 435. No. 2. p. 167891.
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Tugaeva K. V., Sysoev A. A., Kapitonova A. A., Smith J. L. R., Zhu P., COOLEY R. A., Antson A., Sluchanko N. N. Human 14-3-3 Proteins Site-selectively Bind the Mutational Hotspot Region of SARS-CoV-2 Nucleoprotein Modulating its Phosphoregulation // Journal of Molecular Biology. 2023. Vol. 435. No. 2. p. 167891.
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TY - JOUR
DO - 10.1016/j.jmb.2022.167891
UR - https://doi.org/10.1016%2Fj.jmb.2022.167891
TI - Human 14-3-3 Proteins Site-selectively Bind the Mutational Hotspot Region of SARS-CoV-2 Nucleoprotein Modulating its Phosphoregulation
T2 - Journal of Molecular Biology
AU - Tugaeva, Kristina V
AU - Sysoev, Andrey A
AU - Kapitonova, Anna A
AU - Smith, Jake L. R.
AU - Zhu, Phillip
AU - COOLEY, RICHARD A.
AU - Antson, A.A.
AU - Sluchanko, Nikolai N.
PY - 2023
DA - 2023/01/01 00:00:00
PB - Elsevier
SP - 167891
IS - 2
VL - 435
PMID - 36427566
SN - 0022-2836
SN - 1089-8638
ER -
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@article{2023_Tugaeva,
author = {Kristina V Tugaeva and Andrey A Sysoev and Anna A Kapitonova and Jake L. R. Smith and Phillip Zhu and RICHARD A. COOLEY and A.A. Antson and Nikolai N. Sluchanko},
title = {Human 14-3-3 Proteins Site-selectively Bind the Mutational Hotspot Region of SARS-CoV-2 Nucleoprotein Modulating its Phosphoregulation},
journal = {Journal of Molecular Biology},
year = {2023},
volume = {435},
publisher = {Elsevier},
month = {jan},
url = {https://doi.org/10.1016%2Fj.jmb.2022.167891},
number = {2},
pages = {167891},
doi = {10.1016/j.jmb.2022.167891}
}
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MLA
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Tugaeva, Kristina V., et al. “Human 14-3-3 Proteins Site-selectively Bind the Mutational Hotspot Region of SARS-CoV-2 Nucleoprotein Modulating its Phosphoregulation.” Journal of Molecular Biology, vol. 435, no. 2, Jan. 2023, p. 167891. https://doi.org/10.1016%2Fj.jmb.2022.167891.