» Articles » PMID: 38018991

Diversity of Short Linear Interaction Motifs in SARS-CoV-2 Nucleocapsid Protein

Overview
Journal mBio
Specialty Microbiology
Date 2023 Nov 29
PMID 38018991
Authors
Affiliations
Soon will be listed here.
Abstract

Short linear motifs (SLiMs) are 3-10 amino acid long binding motifs in intrinsically disordered protein regions (IDRs) that serve as ubiquitous protein-protein interaction modules in eukaryotic cells. Through molecular mimicry, viruses hijack these sequence motifs to control host cellular processes. It is thought that the small size of SLiMs and the high mutation frequencies of viral IDRs allow rapid host adaptation. However, a salient characteristic of RNA viruses, due to high replication errors, is their obligate existence as mutant swarms. Taking advantage of the uniquely large genomic database of SARS-CoV-2, here, we analyze the role of sequence diversity in the presentation of SLiMs, focusing on the highly abundant, multi-functional nucleocapsid protein. We find that motif mimicry is a highly dynamic process that produces an abundance of motifs transiently present in subsets of mutant species. This diversity allows the virus to efficiently explore eukaryotic motifs and evolve the host-virus interface.

Citing Articles

Modulation of biophysical properties of nucleocapsid protein in the mutant spectrum of SARS-CoV-2.

Nguyen A, Zhao H, Myagmarsuren D, Srinivasan S, Wu D, Chen J Elife. 2024; 13.

PMID: 38941236 PMC: 11213569. DOI: 10.7554/eLife.94836.


Assembly of SARS-CoV-2 nucleocapsid protein with nucleic acid.

Zhao H, Syed A, Khalid M, Nguyen A, Ciling A, Wu D Nucleic Acids Res. 2024; 52(11):6647-6661.

PMID: 38587193 PMC: 11194069. DOI: 10.1093/nar/gkae256.


Protein structure-function continuum model: Emerging nexuses between specificity, evolution, and structure.

Gupta M, Uversky V Protein Sci. 2024; 33(4):e4968.

PMID: 38532700 PMC: 10966358. DOI: 10.1002/pro.4968.


Assembly reactions of SARS-CoV-2 nucleocapsid protein with nucleic acid.

Zhao H, Syed A, Khalid M, Nguyen A, Ciling A, Wu D bioRxiv. 2023; .

PMID: 38045338 PMC: 10690241. DOI: 10.1101/2023.11.22.568361.


Modulation of Biophysical Properties of Nucleocapsid Protein in the Mutant Spectrum of SARS-CoV-2.

Nguyen A, Zhao H, Myagmarsuren D, Srinivasan S, Wu D, Chen J bioRxiv. 2023; .

PMID: 38045241 PMC: 10690151. DOI: 10.1101/2023.11.21.568093.

References
1.
Yang Z, Johnson B, Meliopoulos V, Ju X, Zhang P, Hughes M . Interaction between host G3BP and viral nucleocapsid protein regulates SARS-CoV-2 replication and pathogenicity. Cell Rep. 2024; 43(3):113965. PMC: 11044841. DOI: 10.1016/j.celrep.2024.113965. View

2.
Meszaros B, Samano-Sanchez H, Alvarado-Valverde J, calyseva J, Martinez-Perez E, Alves R . Short linear motif candidates in the cell entry system used by SARS-CoV-2 and their potential therapeutic implications. Sci Signal. 2021; 14(665). PMC: 7928535. DOI: 10.1126/scisignal.abd0334. View

3.
Wu W, Cheng Y, Zhou H, Sun C, Zhang S . The SARS-CoV-2 nucleocapsid protein: its role in the viral life cycle, structure and functions, and use as a potential target in the development of vaccines and diagnostics. Virol J. 2023; 20(1):6. PMC: 9831023. DOI: 10.1186/s12985-023-01968-6. View

4.
Biswal M, Lu J, Song J . SARS-CoV-2 Nucleocapsid Protein Targets a Conserved Surface Groove of the NTF2-like Domain of G3BP1. J Mol Biol. 2022; 434(9):167516. PMC: 8882607. DOI: 10.1016/j.jmb.2022.167516. View

5.
Shuler G, Hagai T . Rapidly evolving viral motifs mostly target biophysically constrained binding pockets of host proteins. Cell Rep. 2022; 40(7):111212. DOI: 10.1016/j.celrep.2022.111212. View