- EMDB-47752: Structural Insights into HIV-1 Vif-Mediated Ubiquitination and De... -
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Entry
Database: EMDB / ID: EMD-47752
Title
Structural Insights into HIV-1 Vif-Mediated Ubiquitination and Degradation of APOBEC3H
Map data
Sample
Complex: Ternary complex of APOBEC3H and Vif of HIV-1
RNA: RNA (5'-R(P*UP*GP*CP*CP*GP*GP*GP*UP*A)-3')
RNA: RNA (5'-R(*AP*UP*AP*CP*CP*CP*GP*GP*CP*A)-3')
Protein or peptide: Core-binding factor subunit beta
Protein or peptide: Virion infectivity factor
Protein or peptide: single-stranded DNA cytosine deaminase
Ligand: ZINC ION
Keywords
APOBEC3H HIV-1 Vif / VIRAL PROTEIN / VIRAL PROTEIN-RNA complex
Function / homology
Function and homology information
RUNX3 regulates RUNX1-mediated transcription / RUNX1 regulates transcription of genes involved in BCR signaling / RUNX1 regulates transcription of genes involved in interleukin signaling / RUNX2 regulates bone development / core-binding factor complex / RUNX1 regulates expression of components of tight junctions / positive regulation of CD8-positive, alpha-beta T cell differentiation / RUNX2 regulates chondrocyte maturation / single-stranded DNA cytosine deaminase / negative regulation of CD4-positive, alpha-beta T cell differentiation ...RUNX3 regulates RUNX1-mediated transcription / RUNX1 regulates transcription of genes involved in BCR signaling / RUNX1 regulates transcription of genes involved in interleukin signaling / RUNX2 regulates bone development / core-binding factor complex / RUNX1 regulates expression of components of tight junctions / positive regulation of CD8-positive, alpha-beta T cell differentiation / RUNX2 regulates chondrocyte maturation / single-stranded DNA cytosine deaminase / negative regulation of CD4-positive, alpha-beta T cell differentiation / clearance of foreign intracellular DNA / RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs) / cytidine deaminase activity / lymphocyte differentiation / RUNX2 regulates genes involved in cell migration / Transcriptional regulation by RUNX2 / RUNX2 regulates genes involved in differentiation of myeloid cells / RUNX1 regulates transcription of genes involved in differentiation of keratinocytes / transposable element silencing / RUNX3 Regulates Immune Response and Cell Migration / myeloid cell differentiation / definitive hemopoiesis / RUNX1 regulates transcription of genes involved in differentiation of myeloid cells / Regulation of RUNX1 Expression and Activity / RUNX1 regulates transcription of genes involved in WNT signaling / RUNX1 regulates estrogen receptor mediated transcription / negative regulation of viral genome replication / RUNX2 regulates osteoblast differentiation / RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known / RUNX3 regulates p14-ARF / viral life cycle / cell maturation / Regulation of RUNX3 expression and activity / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / virion component / Transcriptional regulation of granulopoiesis / protein polyubiquitination / Regulation of RUNX2 expression and activity / osteoblast differentiation / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Estrogen-dependent gene expression / defense response to virus / sequence-specific DNA binding / transcription by RNA polymerase II / host cell cytoplasm / transcription coactivator activity / regulation of transcription by RNA polymerase II / host cell plasma membrane / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / RNA binding / zinc ion binding / nucleoplasm / membrane / cytoplasm Similarity search - Function
National Institutes of Health/National Cancer Institute (NIH/NCI)
R01 AI150478
United States
Citation
Journal: Nat Commun / Year: 2025 Title: HIV-1 vif mediates ubiquitination of the proximal protomer in the APOBEC3H dimer to induce degradation. Authors: Katarzyna A Skorupka / Kazuhiro Matsuoka / Bakar Hassan / Rodolfo Ghirlando / Vanivilasini Balachandran / Ting-Hua Chen / Kylie J Walters / Celia A Schiffer / Matthias Wolf / Yasumasa ...Authors: Katarzyna A Skorupka / Kazuhiro Matsuoka / Bakar Hassan / Rodolfo Ghirlando / Vanivilasini Balachandran / Ting-Hua Chen / Kylie J Walters / Celia A Schiffer / Matthias Wolf / Yasumasa Iwatani / Hiroshi Matsuo / Abstract: The APOBEC3 family of cytidine deaminases restricts retroviruses like HIV-1 by mutating viral DNA. HIV-1 evades this restriction by producing Vif, which recruits the Cullin-5 (CUL5) E3 ubiquitin ...The APOBEC3 family of cytidine deaminases restricts retroviruses like HIV-1 by mutating viral DNA. HIV-1 evades this restriction by producing Vif, which recruits the Cullin-5 (CUL5) E3 ubiquitin ligase complex to promote APOBEC3 degradation. Here we resolve key aspects of this counter-defense mechanism by determining a 3.6 Å cryo-EM structure of chimpanzee APOBEC3H (cpzA3H) in complex with HIV-1 Vif and three components of the CUL5 E3 ligase-CBFβ, EloB, and EloC (VCBC). The structure captures cpzA3H as an RNA-mediated dimer within the cpzA3H-VCBC complex, allowing us to examine the role of dimerization. We find that ubiquitination occurs specifically at two lysine residues on the Vif-proximal protomer, while the distal protomer remains unmodified. The structural model of the active cpzA3H-Vif-CUL5 E3 ligase holoenzyme reveals spatial preferences for ubiquitin transfer to the targeted lysine residues. These findings enhance our understanding of A3H degradation and suggest new antiviral strategies targeting this host-virus interface.
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