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Basic Characteristics of Mutations
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Mutation Site
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I51A-S52A |
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Mutation Site Sentence
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In addition, we included double mutants P49A–K50A and I51–S52A, because of their proximity to other double mutants that showed significant defects in CBFβ binding. |
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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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Vif |
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Standardized Encoding Gene
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Vif
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Genotype/Subtype
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HIV-1 |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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HIV Infections
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Immune
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- |
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Target Gene
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CBFB
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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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28302150
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Title
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Identification of a tripartite interaction between the N-terminus of HIV-1 Vif and CBFbeta that is critical for Vif function
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Author
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Desimmie BA,Smith JL,Matsuo H,Hu WS,Pathak VK
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Journal
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Retrovirology
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Journal Info
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2017 Mar 17;14(1):19
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Abstract
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BACKGROUND: HIV-1 Vif interacts with the cellular core-binding factor beta (CBFbeta) and counteracts the protective roles of certain human APOBEC3 (A3) proteins by targeting them for proteasomal degradation. Previous studies have identified some amino acids important for Vif-CBFbeta interactions, and recently a co-crystal structure of a pentameric complex of HIV-1 Vif, CBFbeta, Cul5, EloB, and EloC was resolved. However, a comprehensive analysis of Vif-CBFbeta interactions that are important for Vif function has not been performed. RESULTS: Here, we carried out double-alanine scanning mutagenesis of the first 60 amino acids of Vif and determined their effects on interaction with CBFbeta and their ability to induce A3G degradation as well as rescue HIV-1 replication in the presence of A3G. We found that multiple Vif residues are involved in the extensive N-terminal Vif-CBFbeta interaction and that the (5)WQVMIVW(11) region of Vif is the major determinant. A minimum of three alanine substitutions are required to completely abrogate the Vif-CBFbeta interaction and Vif's ability to rescue HIV-1 infectivity in the presence of A3G. Mutational analysis of CBFbeta revealed that F68 and I55 residues are important and participate in a tripartite hydrophobic interaction with W5 of Vif to maintain a stable and functional Vif-CBFbeta complex. We also determined that CBFbeta amino acids (73)WQGEQR(78), which are not resolved in the structure of the pentameric complex, are not involved in interaction with HIV-1 Vif. CONCLUSIONS: Our results provide detailed insight into the Vif-CBFbeta interactions that are critical for Vif function and may contribute to the rational design of HIV-1 inhibitors that block Vif-mediated degradation of A3 proteins.
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Sequence Data
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-
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