- EMDB-29488: Human APOBEC3H bound to HIV-1 Vif in complex with CBF-beta, ELOB,... -
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基本情報
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データベース: EMDB / ID: EMD-29488
タイトル
Human APOBEC3H bound to HIV-1 Vif in complex with CBF-beta, ELOB, ELOC, and CUL5
マップデータ
試料
複合体: Hetero-hexameric complex of HIV-1 Vif and human APOBEC3H, CBF-beta, ELOB, ELOC, and CUL5
タンパク質・ペプチド: Core-binding factor subunit beta
タンパク質・ペプチド: Virion infectivity factor
タンパク質・ペプチド: DNA dC->dU-editing enzyme APOBEC-3H
RNA: RNA(5'-R(AP*UP*UP*UP*UP*UP*UP*UP*UP*U)-3')
RNA: RNA(5'-R(*AP*AP*AP*AP*AP*AP*AP*AP*A)-3')
タンパク質・ペプチド: Cullin 5
タンパク質・ペプチド: Elongin-B
タンパク質・ペプチド: Elongin-C
リガンド: ZINC ION
リガンド: water
キーワード
virus-host protein complex / ANTIVIRAL PROTEIN
機能・相同性
機能・相同性情報
RUNX3 regulates RUNX1-mediated transcription / RUNX1 regulates transcription of genes involved in BCR signaling / mRNA Editing: C to U Conversion / Formation of the Editosome / 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 ...RUNX3 regulates RUNX1-mediated transcription / RUNX1 regulates transcription of genes involved in BCR signaling / mRNA Editing: C to U Conversion / Formation of the Editosome / 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 / DNA cytosine deamination / lymphocyte differentiation / negative regulation by host of viral genome replication / cytidine to uridine editing / clearance of foreign intracellular DNA / cytidine deaminase activity / RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs) / negative regulation of single stranded viral RNA replication via double stranded DNA intermediate / RUNX2 regulates genes involved in cell migration / RUNX2 regulates genes involved in differentiation of myeloid cells / Transcriptional regulation by RUNX2 / transposable element silencing / RUNX1 regulates transcription of genes involved in differentiation of keratinocytes / myeloid cell differentiation / target-directed miRNA degradation / RUNX3 Regulates Immune Response and Cell Migration / elongin complex / VCB complex / definitive hemopoiesis / RUNX1 regulates transcription of genes involved in differentiation of myeloid cells / Regulation of RUNX1 Expression and Activity / Cul5-RING ubiquitin ligase complex / SCF ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / RUNX1 regulates transcription of genes involved in WNT signaling / RUNX1 regulates estrogen receptor mediated transcription / RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known / RUNX2 regulates osteoblast differentiation / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / RUNX3 regulates p14-ARF / Tat-mediated elongation of the HIV-1 transcript / Formation of HIV-1 elongation complex containing HIV-1 Tat / Formation of HIV elongation complex in the absence of HIV Tat / RNA Polymerase II Transcription Elongation / Formation of RNA Pol II elongation complex / cell maturation / RNA Polymerase II Pre-transcription Events / viral life cycle / transcription corepressor binding / TP53 Regulates Transcription of DNA Repair Genes / transcription initiation at RNA polymerase II promoter / transcription elongation by RNA polymerase II / virion component / Vif-mediated degradation of APOBEC3G / Regulation of RUNX3 expression and activity / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / P-body / Inactivation of CSF3 (G-CSF) signaling / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Evasion by RSV of host interferon responses / Regulation of expression of SLITs and ROBOs / Transcriptional regulation of granulopoiesis / osteoblast differentiation / protein polyubiquitination / Regulation of RUNX2 expression and activity / Antigen processing: Ubiquitination & Proteasome degradation / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Neddylation / protein-macromolecule adaptor activity / ubiquitin-dependent protein catabolic process / protein-containing complex assembly / defense response to virus / Estrogen-dependent gene expression / sequence-specific DNA binding / host cell cytoplasm / transcription by RNA polymerase II / transcription coactivator activity / protein ubiquitination / innate immune response / ubiquitin protein ligase binding / 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 / nucleus / cytosol / cytoplasm 類似検索 - 分子機能
APOBEC3H / APOBEC3 / Retroviral Vif (Viral infectivity) protein / Retroviral Vif (Viral infectivity) protein / Core-binding factor, beta subunit / Core-binding factor, beta subunit superfamily / Core binding factor beta subunit / : / APOBEC/CMP deaminase, zinc-binding / Cytidine and deoxycytidylate deaminases zinc-binding region signature. ...APOBEC3H / APOBEC3 / Retroviral Vif (Viral infectivity) protein / Retroviral Vif (Viral infectivity) protein / Core-binding factor, beta subunit / Core-binding factor, beta subunit superfamily / Core binding factor beta subunit / : / APOBEC/CMP deaminase, zinc-binding / Cytidine and deoxycytidylate deaminases zinc-binding region signature. / Cytidine and deoxycytidylate deaminase domain / Cytidine and deoxycytidylate deaminases domain profile. / Cullin protein neddylation domain / Elongin B / Elongin-C / Cytidine deaminase-like / Cullin, conserved site / Cullin family signature. / Cullin repeat-like-containing domain superfamily / Cullin protein, neddylation domain / Cullin / Cullin protein neddylation domain / Cullin / Cullin, N-terminal / Cullin homology domain / Cullin homology domain superfamily / Cullin family / Cullin family profile. / S-phase kinase-associated protein 1-like / SKP1 component, POZ domain / Skp1 family, tetramerisation domain / Found in Skp1 protein family / SKP1/BTB/POZ domain superfamily / Ubiquitin family / Ubiquitin homologues / Ubiquitin domain profile. / Ubiquitin-like domain / Ubiquitin-like domain superfamily / Winged helix DNA-binding domain superfamily / Winged helix-like DNA-binding domain superfamily 類似検索 - ドメイン・相同性
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01AI150524
米国
引用
ジャーナル: Nat Commun / 年: 2023 タイトル: Structural basis of HIV-1 Vif-mediated E3 ligase targeting of host APOBEC3H. 著者: Fumiaki Ito / Ana L Alvarez-Cabrera / Kyumin Kim / Z Hong Zhou / Xiaojiang S Chen / 要旨: Human APOBEC3 (A3) cytidine deaminases are antiviral factors that are particularly potent against retroviruses. As a countermeasure, HIV-1 uses a viral infectivity factor (Vif) to target specific ...Human APOBEC3 (A3) cytidine deaminases are antiviral factors that are particularly potent against retroviruses. As a countermeasure, HIV-1 uses a viral infectivity factor (Vif) to target specific human A3s for proteasomal degradation. Vif recruits cellular transcription cofactor CBF-β and Cullin-5 (CUL5) RING E3 ubiquitin ligase to bind different A3s distinctively, but how this is accomplished remains unclear in the absence of the atomic structure of the complex. Here, we present the cryo-EM structures of HIV-1 Vif in complex with human A3H, CBF-β and components of CUL5 ubiquitin ligase (CUL5, ELOB, and ELOC). Vif nucleates the entire complex by directly binding four human proteins, A3H, CBF-β, CUL5, and ELOC. The structures reveal a large interface area between A3H and Vif, primarily mediated by an α-helical side of A3H and a five-stranded β-sheet of Vif. This A3H-Vif interface unveils the basis for sensitivity-modulating polymorphism of both proteins, including a previously reported gain-of-function mutation in Vif isolated from HIV/AIDS patients. Our structural and functional results provide insights into the remarkable interplay between HIV and humans and would inform development efforts for anti-HIV therapeutics.