Evidence map›Paper›PMID 38941236›Full record

ArticleeLife2024

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

Ai Nguyen, Huaying Zhao, Dulguun Myagmarsuren, Sanjana Srinivasan, Di Wu, Jiji Chen, Grzegorz Piszczek, Peter Schuck

Abstract read
In one paragraph

Article in eLife, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed.

  1. Article
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  10. Evolution of a fuzzy ribonucleoprotein complex in viral assembly.bioRxiv : the preprint server for biology · 2025
    Article
  11. Article
  12. Article
  13. Article
  14. Protein-RNA condensation kinetics via filamentous nanoclusters.Protein science : a publication of the Protein Society · 2025
    Article
  15. Article
  16. Review
  17. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Ai NguyenLaboratory of Dynamics of Macromolecular Assembly, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, United States.
Huaying ZhaoLaboratory of Dynamics of Macromolecular Assembly, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, United States.ORCID https://orcid.org/0000-0002-8827-6639
Dulguun MyagmarsurenLaboratory of Dynamics of Macromolecular Assembly, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, United States.
Sanjana SrinivasanLaboratory of Dynamics of Macromolecular Assembly, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, United States.
Di WuBiophysics Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, United States.
Jiji ChenAdvanced Imaging and Microscopy Resource, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, United States.
Grzegorz PiszczekBiophysics Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, United States.
Peter SchuckLaboratory of Dynamics of Macromolecular Assembly, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, United States.ORCID https://orcid.org/0000-0002-8859-6966

Funding

The mutational landscape of SARS-CoV-2 nucleocapsid proteinZIAEB000099 · NIBIB · NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING · PI SCHUCK, PETER · 2022 to 2025
$2.0M
Advanced Imaging and Microscopy Shared ResourceZICEB000104 · NIBIB · NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING · PI VISHWASRAO, HARSHAD · 2024 to 2025
$1.3M
Intramural NIH HHS ZIA EB000099NIH HHS ZIA EB000099-02
6 · The paper itself

Abstract

Genetic diversity is a hallmark of RNA viruses and the basis for their evolutionary success. Taking advantage of the uniquely large genomic database of SARS-CoV-2, we examine the impact of mutations across the spectrum of viable amino acid sequences on the biophysical phenotypes of the highly expressed and multifunctional nucleocapsid protein. We find variation in the physicochemical parameters of its extended intrinsically disordered regions (IDRs) sufficient to allow local plasticity, but also observe functional constraints that similarly occur in related coronaviruses. In biophysical experiments with several N-protein species carrying mutations associated with major variants, we find that point mutations in the IDRs can have nonlocal impact and modulate thermodynamic stability, secondary structure, protein oligomeric state, particle formation, and liquid-liquid phase separation. In the Omicron variant, distant mutations in different IDRs have compensatory effects in shifting a delicate balance of interactions controlling protein assembly properties, and include the creation of a new protein-protein interaction interface in the N-terminal IDR through the defining P13L mutation. A picture emerges where genetic diversity is accompanied by significant variation in biophysical characteristics of functional N-protein species, in particular in the IDRs.

Indexed as

Coronavirus Nucleocapsid ProteinsMutationSARS-CoV-2COVID-19HumansIntrinsically Disordered ProteinsNucleocapsid ProteinsPhosphoproteinsProtein StabilityThermodynamicsCoronavirus Nucleocapsid ProteinsIntrinsically Disordered Proteinsnucleocapsid phosphoprotein, SARS-CoV-2Nucleocapsid ProteinsPhosphoproteinsbiophysical fitness landscapegenotype-phenotype relationshipinfectious diseaseintrinsically disordered proteinmicrobiologymolecular biophysicsmutant spectrumprotein evolutionSARS-CoV-2structural biologyviruses

Identifiers

PMID38941236
PMCPMC11213569

What OpenQuestion holds

Textmetadata
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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.