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Basic Characteristics of Mutations
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Mutation Site
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A119S |
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Mutation Site Sentence
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We found that nat_mutants could–as a proxy–be divided into two groups according to the distribution of CSDs: NTDs A119S, E136D and P151S show exclusively local effects induced by their respective mutations, while P67S, D63G and P80R display more pronounced and long-range CSDs (Fig. 2a and Supplementary Fig. 2a), suggesting those two groups of mutants could differentially modulate RNA-binding of the NTD. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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NTD |
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Standardized Encoding Gene
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|
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Genotype/Subtype
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Zeta |
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Viral Reference
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NC_045512.2
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Functional Impact and Mechanisms
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Disease
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COVID-19
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Immune
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- |
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Target Gene
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-
|
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
|
- |
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Location
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- |
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Literature Information
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PMID
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39653699
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Title
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A core network in the SARS-CoV-2 nucleocapsid NTD mediates structural integrity and selective RNA-binding
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Author
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Dhamotharan K,Korn SM,Wacker A,Becker MA,Gunther S,Schwalbe H,Schlundt A
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Journal
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Nature communications
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Journal Info
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2024 Dec 9;15(1):10656
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Abstract
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The SARS-CoV-2 nucleocapsid protein is indispensable for viral RNA genome processing. Although the N-terminal domain (NTD) is suggested to mediate specific RNA-interactions, high-resolution structures with viral RNA are still lacking. Available hybrid structures of the NTD with ssRNA and dsRNA provide valuable insights; however, the precise mechanism of complex formation remains elusive. Similarly, the molecular impact of nucleocapsid NTD mutations that have emerged since 2019 has not yet been fully explored. Using crystallography and solution NMR, we investigate how NTD mutations influence structural integrity and RNA-binding. We find that both features rely on a core network of residues conserved in Betacoronaviruses, crucial for protein stability and communication among flexible loop-regions that facilitate RNA-recognition. Our comprehensive structural analysis demonstrates that contacts within this network guide selective RNA-interactions. We propose that the core network renders the NTD evolutionarily robust in stability and plasticity for its versatile RNA processing roles.
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Sequence Data
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-
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