Journal of Molecular Biology, volume 433, issue 8, pages 166875

The Mechanism of SARS-CoV-2 Nucleocapsid Protein Recognition by the Human 14-3-3 Proteins

Tugaeva Kristina V ¹

Hawkins Dorothy E D P ²

Smith Jake L R ²

Bayfield Oliver W ²

Ker De-Sheng ²

Sysoev Andrey A. ¹

Klychnikov Oleg I. ³

Antson A.A. ²

Sluchanko Nikolai N. ¹

Hide authors affiliations Show authors affiliations: 3 affiliations

A.N. Bach Institute of Biochemistry, Federal Research Center of Biotechnology of the Russian Academy of Sciences, 119071, Moscow, Russia

Bach Institute of Biochemistry of the Russian Academy of Sciences

Federal Research Centre “Fundamentals of Biotechnology” of the Russian Academy of Sciences

York Structural Biology Laboratory, Department of Chemistry, University of York, York YO10 5DD, United Kingdom. |

Department of Biochemistry, School of Biology, M.V. Lomonosov Moscow State University, 119991 Moscow, Russia. |

Publication type: Journal Article

Publication date: 2021-04-01

Elsevier

Journal: Journal of Molecular Biology

Quartile SCImago

Quartile WOS

Impact factor: 5.6

ISSN: 00222836, 10898638

DOI: 10.1016/j.jmb.2021.166875

Copy DOI

PubMed ID: 33556408

Molecular Biology

Structural Biology

Abstract

The coronavirus nucleocapsid protein (N) controls viral genome packaging and contains numerous phosphorylation sites located within unstructured regions. Binding of phosphorylated SARS-CoV N to the host 14-3-3 protein in the cytoplasm was reported to regulate nucleocytoplasmic N shuttling. All seven isoforms of the human 14-3-3 are abundantly present in tissues vulnerable to SARS-CoV-2, where N can constitute up to ~1% of expressed proteins during infection. Although the association between 14-3-3 and SARS-CoV-2 N proteins can represent one of the key host-pathogen interactions, its molecular mechanism and the specific critical phosphosites are unknown. Here, we show that phosphorylated SARS-CoV-2 N protein (pN) dimers, reconstituted via bacterial co-expression with protein kinase A, directly associate, in a phosphorylation-dependent manner, with the dimeric 14-3-3 protein, but not with its monomeric mutant. We demonstrate that pN is recognized by all seven human 14-3-3 isoforms with various efficiencies and deduce the apparent KD to selected isoforms, showing that these are in a low micromolar range. Serial truncations pinpointed a critical phosphorylation site to Ser197, which is conserved among related zoonotic coronaviruses and located within the functionally important, SR-rich region of N. The relatively tight 14-3-3/pN association could regulate nucleocytoplasmic shuttling and other functions of N via occlusion of the SR-rich region, and could also hijack cellular pathways by 14-3-3 sequestration. As such, the assembly may represent a valuable target for therapeutic intervention.

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Citations by journals

	1 2 3
Wellcome Open Research	Wellcome Open Research, 3, 5.26% Wellcome Open Research 3 publications, 5.26%
Frontiers in Immunology	Frontiers in Immunology, 3, 5.26% Frontiers in Immunology 3 publications, 5.26%
Virology Journal	Virology Journal, 2, 3.51% Virology Journal 2 publications, 3.51%
International Journal of Biological Macromolecules	International Journal of Biological Macromolecules, 2, 3.51% International Journal of Biological Macromolecules 2 publications, 3.51%
Journal of Molecular Biology	Journal of Molecular Biology, 1, 1.75% Journal of Molecular Biology 1 publication, 1.75%
Molecular and Cellular Proteomics	Molecular and Cellular Proteomics, 1, 1.75% Molecular and Cellular Proteomics 1 publication, 1.75%
PeerJ	PeerJ, 1, 1.75% PeerJ 1 publication, 1.75%
Viruses	Viruses, 1, 1.75% Viruses 1 publication, 1.75%
Diagnostics	Diagnostics, 1, 1.75% Diagnostics 1 publication, 1.75%
Frontiers in Pharmacology	Frontiers in Pharmacology, 1, 1.75% Frontiers in Pharmacology 1 publication, 1.75%
Frontiers in Microbiology	Frontiers in Microbiology, 1, 1.75% Frontiers in Microbiology 1 publication, 1.75%
Cell Biochemistry and Biophysics	Cell Biochemistry and Biophysics, 1, 1.75% Cell Biochemistry and Biophysics 1 publication, 1.75%
Science advances	Science advances, 1, 1.75% Science advances 1 publication, 1.75%
Informatics in Medicine Unlocked	Informatics in Medicine Unlocked, 1, 1.75% Informatics in Medicine Unlocked 1 publication, 1.75%
ACS Central Science	ACS Central Science, 1, 1.75% ACS Central Science 1 publication, 1.75%
Journal of Structural Biology	Journal of Structural Biology, 1, 1.75% Journal of Structural Biology 1 publication, 1.75%
Trends in Microbiology	Trends in Microbiology, 1, 1.75% Trends in Microbiology 1 publication, 1.75%
Molecular Therapy - Nucleic Acids	Molecular Therapy - Nucleic Acids, 1, 1.75% Molecular Therapy - Nucleic Acids 1 publication, 1.75%
PLoS Pathogens	PLoS Pathogens, 1, 1.75% PLoS Pathogens 1 publication, 1.75%
Journal of Biological Chemistry	Journal of Biological Chemistry, 1, 1.75% Journal of Biological Chemistry 1 publication, 1.75%
Biochemical and Biophysical Research Communications	Biochemical and Biophysical Research Communications, 1, 1.75% Biochemical and Biophysical Research Communications 1 publication, 1.75%
Journal of Cellular and Molecular Medicine	Journal of Cellular and Molecular Medicine, 1, 1.75% Journal of Cellular and Molecular Medicine 1 publication, 1.75%
Pharmacology Research and Perspectives	Pharmacology Research and Perspectives, 1, 1.75% Pharmacology Research and Perspectives 1 publication, 1.75%
Protein Science	Protein Science, 1, 1.75% Protein Science 1 publication, 1.75%
ACS Measurement Science Au	ACS Measurement Science Au, 1, 1.75% ACS Measurement Science Au 1 publication, 1.75%
Biochimie	Biochimie, 1, 1.75% Biochimie 1 publication, 1.75%
Heliyon	Heliyon, 1, 1.75% Heliyon 1 publication, 1.75%
Journal of Biomolecular Structure and Dynamics	Journal of Biomolecular Structure and Dynamics, 1, 1.75% Journal of Biomolecular Structure and Dynamics 1 publication, 1.75%
PNAS Nexus	PNAS Nexus, 1, 1.75% PNAS Nexus 1 publication, 1.75%
	1 2 3

Citations by publishers

	2 4 6 8 10 12
Elsevier	Elsevier, 11, 19.3% Elsevier 11 publications, 19.3%
Springer Nature	Springer Nature, 5, 8.77% Springer Nature 5 publications, 8.77%
Frontiers Media S.A.	Frontiers Media S.A., 5, 8.77% Frontiers Media S.A. 5 publications, 8.77%
Taylor & Francis	Taylor & Francis, 4, 7.02% Taylor & Francis 4 publications, 7.02%
Multidisciplinary Digital Publishing Institute (MDPI)	Multidisciplinary Digital Publishing Institute (MDPI), 3, 5.26% Multidisciplinary Digital Publishing Institute (MDPI) 3 publications, 5.26%
Wiley	Wiley, 3, 5.26% Wiley 3 publications, 5.26%
American Society for Biochemistry and Molecular Biology	American Society for Biochemistry and Molecular Biology, 2, 3.51% American Society for Biochemistry and Molecular Biology 2 publications, 3.51%
American Chemical Society (ACS)	American Chemical Society (ACS), 2, 3.51% American Chemical Society (ACS) 2 publications, 3.51%
Oxford University Press	Oxford University Press, 2, 3.51% Oxford University Press 2 publications, 3.51%
PeerJ	PeerJ, 1, 1.75% PeerJ 1 publication, 1.75%
American Association for the Advancement of Science (AAAS)	American Association for the Advancement of Science (AAAS), 1, 1.75% American Association for the Advancement of Science (AAAS) 1 publication, 1.75%
Public Library of Science (PLoS)	Public Library of Science (PLoS), 1, 1.75% Public Library of Science (PLoS) 1 publication, 1.75%
American Society for Microbiology	American Society for Microbiology, 1, 1.75% American Society for Microbiology 1 publication, 1.75%
	2 4 6 8 10 12

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Tugaeva K. V. et al. The Mechanism of SARS-CoV-2 Nucleocapsid Protein Recognition by the Human 14-3-3 Proteins // Journal of Molecular Biology. 2021. Vol. 433. No. 8. p. 166875.

GOST all authors (up to 50) Copy

Tugaeva K. V., Hawkins D. E. D. P., Smith J. L. R., Bayfield O. W., Ker D., Sysoev A. A., Klychnikov O. I., Antson A., Sluchanko N. N. The Mechanism of SARS-CoV-2 Nucleocapsid Protein Recognition by the Human 14-3-3 Proteins // Journal of Molecular Biology. 2021. Vol. 433. No. 8. p. 166875.

RIS |

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RIS Copy

TY - JOUR

DO - 10.1016/j.jmb.2021.166875

UR - https://doi.org/10.1016%2Fj.jmb.2021.166875

TI - The Mechanism of SARS-CoV-2 Nucleocapsid Protein Recognition by the Human 14-3-3 Proteins

T2 - Journal of Molecular Biology

AU - Tugaeva, Kristina V

AU - Hawkins, Dorothy E D P

AU - Smith, Jake L R

AU - Bayfield, Oliver W

AU - Ker, De-Sheng

AU - Sysoev, Andrey A.

AU - Klychnikov, Oleg I.

AU - Antson, A.A.

AU - Sluchanko, Nikolai N.

PY - 2021

DA - 2021/04/01 00:00:00

PB - Elsevier

SP - 166875

IS - 8

VL - 433

PMID - 33556408

SN - 0022-2836

SN - 1089-8638

ER -

BibTex |

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@article{2021_Tugaeva,

author = {Kristina V Tugaeva and Dorothy E D P Hawkins and Jake L R Smith and Oliver W Bayfield and De-Sheng Ker and Andrey A. Sysoev and Oleg I. Klychnikov and A.A. Antson and Nikolai N. Sluchanko},

title = {The Mechanism of SARS-CoV-2 Nucleocapsid Protein Recognition by the Human 14-3-3 Proteins},

journal = {Journal of Molecular Biology},

year = {2021},

volume = {433},

publisher = {Elsevier},

month = {apr},

url = {https://doi.org/10.1016%2Fj.jmb.2021.166875},

number = {8},

pages = {166875},

doi = {10.1016/j.jmb.2021.166875}

}

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MLA Copy

Tugaeva, Kristina V., et al. “The Mechanism of SARS-CoV-2 Nucleocapsid Protein Recognition by the Human 14-3-3 Proteins.” Journal of Molecular Biology, vol. 433, no. 8, Apr. 2021, p. 166875. https://doi.org/10.1016%2Fj.jmb.2021.166875.

Found error?

Publisher

Elsevier

Journal

Journal of Molecular Biology

Quartile SCImago

Quartile WOS

Impact factor

5.6

ISSN

00222836 (Print)
10898638 (Electronic)

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