RABV Mutation Detail Information

Virus Mutation RABV Mutation S389E


Basic Characteristics of Mutations
Mutation Site S389E
Mutation Site Sentence Nevertheless, a triple mutant shows 3.5-fold stronger affinity for PCTD than the full-length S389E N protein.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region N
Standardized Encoding Gene RABVgp1  
Genotype/Subtype -
Viral Reference -
Functional Impact and Mechanisms
Disease -
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location -
Literature Information
PMID 39736335
Title Analysis of mechanisms of the rabies virus P protein-nucleocapsid interaction using engineered N-protein peptides and potential applications in antivirals design
Author Zhan J,Chakraborty S,Sethi A,Mok YF,Yan F,Moseley GW,Gooley PR
Journal Antiviral research
Journal Info 2025 Feb;234:106075
Abstract The Phosphoprotein (P protein) of the rabies virus has multiple roles in virus replication. A critical function is to act as a cofactor in genome replication and mRNA production through binding via its N-terminal region to the L protein, the essential enzyme for mRNA and genome synthesis/processing, and via its C-terminal domain (P(CTD)) to the N protein and viral RNA (N-RNA) ribonucleoprotein complex. The binding site of the P(CTD) on the N protein is a disordered loop that is expected to be phosphorylated at Ser389. This interface may provide novel targets for antiviral approaches. Following an alanine scan of the peptide we selected two single site mutations that showed improved affinity and combined these mutations with a phosphomimetic (S389E) to produce double and triple mutants in the context of linear and cyclic peptides of the disordered loop, with the goal of generating a competitive peptide against the N-RNA complex. To assess the binding properties of the peptides we characterized their thermodynamics identifying complex properties of improved enthalpy but with compensating entropy for mutants and cyclized peptides. Nevertheless, a triple mutant shows 3.5-fold stronger affinity for P(CTD) than the full-length S389E N protein. Structural characterization of the triple mutant suggests the improved affinity may be due to trapping a favoured beta-strand structure for binding to the P(CTD). This novel peptide may serve as a template for the future design of antivirals.
Sequence Data -
Mutation Information
Note
Basic Characteristics of Mutations
  • Mutation Site: The specific location in a gene or protein sequence where a change occurs.
  • Mutation Level: The level at which a mutation occurs, including the nucleotide or amino acid level.
  • Mutation Type: The nature of the mutation, such as missense mutation, nonsense mutation, synonymous mutation, etc.
  • Gene/Protein/Region: Refers to the specific region of the virus where the mutation occurs. Including viral genes, viral proteins, or a specific viral genome region. If the article does not specifically indicate the relationship between the mutation and its correspondence, the main
  • Gene/Protein/Region studied in the article is marked.
  • Genotype/Subtype: Refers to the viral genotype or subtype where the mutation occurs. If the article does not specifically indicate the relationship between the mutation and its correspondence, the main Genotype/Subtype studied in the article is marked.
  • Viral Reference: Refers to the standard virus strain used to compare and analyze viral sequences.
Functional Impact and Mechanisms
  • Disease: An abnormal physiological state with specific symptoms and signs caused by viral infection.
  • Immune: The article focuses on the study of mutations and immune.
  • Target Gene: Host genes that viral mutations may affect.
Clinical and Epidemiological Correlations
  • Clinical Information: The study is a clinical or epidemiological study and provides basic information about the population.
  • Treatment: The study mentioned a certain treatment method, such as drug resistance caused by mutations. If the study does not specifically indicate the relationship between mutations and their correspondence treatment, the main treatment studied in the article is marked.
  • Location: The source of the research data.
Literature Information
  • Sequence Data: The study provides the data accession number.