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Basic Characteristics of Mutations
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Mutation Site
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Y109A |
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Mutation Site Sentence
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Our RNA-binding data for des_mutants R107A and Y109A confirm the role of both the electrostatic surface potential and central interface residues, likely involved in stacking interactions with RNA as suggested for MHV N-NTD and HCoV-OC43 N-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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- |
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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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- |
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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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