HSV1 Mutation Detail Information

Virus Mutation HSV1 Mutation L28A


Basic Characteristics of Mutations
Mutation Site L28A
Mutation Site Sentence Molecular dynamics simulations and subsequent energetic analyses of the gD-receptor complexes reveal that some mutations (M11A, N15A, L28A, T29A) play a more prominent role for HVEM binding than for nectin-1 binding, thereby conferring specificity to receptor recognition.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region gD
Standardized Encoding Gene US6  
Genotype/Subtype -
Viral Reference -
Functional Impact and Mechanisms
Disease Herpes simplex    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location -
Literature Information
PMID 24647818
Title Mutations in herpes simplex virus gD protein affect receptor binding by different molecular mechanisms
Author Stump JD,Sticht H
Journal Journal of molecular modeling
Journal Info 2014 Apr;20(4):2192
Abstract Glycoprotein D (gD) is an essential protein of herpes simplex virus-1 (HSV-1) that targets the structurally unrelated receptors HVEM and nectin-1. Receptor binding of gD is accompanied by intramolecular structural rearrangements including the detachment of the C-terminus or formation of an N-terminal hairpin structure. We have investigated several gD mutations that were reported to affect receptor binding affinity or specificity in order to identify their molecular mode of action. Molecular dynamics simulations and subsequent energetic analyses of the gD-receptor complexes reveal that some mutations (M11A, N15A, L28A, T29A) play a more prominent role for HVEM binding than for nectin-1 binding, thereby conferring specificity to receptor recognition. However, our studies show that mutations can also affect the intramolecular structural rearrangement processes in gD. W294A and Q27A mutations facilitate the detachment of the C-terminus, and Q27A additionally hampers the formation of an intramolecular hairpin in gD that is exclusively established upon HVEM binding. The finding that a Q27A mutation affects multiple steps of the receptor binding process offers a molecular explanation for its enhanced nectin-1 affinity and the pronounced receptor specificity. This study also indicates that an inspection of the gD-receptor interfaces alone may be insufficient for predicting the effect of novel mutations that alter receptor specificity. Instead, such an analysis will additionally require to assess the effect of candidate mutation on the preceding steps of gD activation.
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.