HIV Mutation Detail Information

Virus Mutation HIV Mutation D474N


Basic Characteristics of Mutations
Mutation Site D474N
Mutation Site Sentence We replaced HIV-1 consensus inner domain residues in the clade B HIV-1YU2 Env with the residues that specifically coevolved with H375 in CRF01_AE strains (Y61H, H105Q, I108V, D474N, M475I, R476K).
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region gp120
Standardized Encoding Gene Env  
Genotype/Subtype HIV-1 B
Viral Reference HXBc2
Functional Impact and Mechanisms
Disease HIV Infections    
Immune Y
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment Env gp120 consensus
Location "Montreal, Canada"
Literature Information
PMID 32457241
Title The HIV-1 Env gp120 Inner Domain Shapes the Phe43 Cavity and the CD4 Binding Site
Author Prevost J,Tolbert WD,Medjahed H,Sherburn RT,Madani N,Zoubchenok D,Gendron-Lepage G,Gaffney AE,Grenier MC,Kirk S,Vergara N,Han C,Mann BT,Chenine AL,Ahmed A,Chaiken I,Kirchhoff F,Hahn BH,Haim H,Abrams CF,Smith AB 3rd,Sodroski J,Pazgier M,Finzi A
Journal mBio
Journal Info 2020 May 26;11(3):e00280-20
Abstract The HIV-1 envelope glycoproteins (Env) undergo conformational changes upon interaction of the gp120 exterior glycoprotein with the CD4 receptor. The gp120 inner domain topological layers facilitate the transition of Env to the CD4-bound conformation. CD4 engages gp120 by introducing its phenylalanine 43 (Phe43) in a cavity (""the Phe43 cavity"") located at the interface between the inner and outer gp120 domains. Small CD4-mimetic compounds (CD4mc) can bind within the Phe43 cavity and trigger conformational changes similar to those induced by CD4. Crystal structures of CD4mc in complex with a modified CRF01_AE gp120 core revealed the importance of these gp120 inner domain layers in stabilizing the Phe43 cavity and shaping the CD4 binding site. Our studies reveal a complex interplay between the gp120 inner domain and the Phe43 cavity and generate useful information for the development of more-potent CD4mc.IMPORTANCE The Phe43 cavity of HIV-1 envelope glycoproteins (Env) is an attractive druggable target. New promising compounds, including small CD4 mimetics (CD4mc), were shown to insert deeply into this cavity. Here, we identify a new network of residues that helps to shape this highly conserved CD4 binding pocket and characterize the structural determinants responsible for Env sensitivity to small CD4 mimetics.
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.