[English] 日本語
Yorodumi- PDB-8fvi: Human APOBEC3H bound to HIV-1 Vif in complex with CBF-beta, ELOB,... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8fvi | ||||||
---|---|---|---|---|---|---|---|
Title | Human APOBEC3H bound to HIV-1 Vif in complex with CBF-beta, ELOB, ELOC, and CUL5 | ||||||
Components |
| ||||||
Keywords | ANTIVIRAL PROTEIN / virus-host protein complex | ||||||
Function / homology | Function and homology information 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 / P-body / Vif-mediated degradation of APOBEC3G / Regulation of RUNX3 expression and activity / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / 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 / osteoblast differentiation / Transcriptional regulation of granulopoiesis / 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 Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Human immunodeficiency virus 1 Escherichia coli (E. coli) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.24 Å | ||||||
Authors | Ito, F. / Alvarez-Cabrera, A.L. / Zhou, Z.H. / Chen, X.S. | ||||||
Funding support | United States, 1items
| ||||||
Citation | Journal: Nat Commun / Year: 2023 Title: Structural basis of HIV-1 Vif-mediated E3 ligase targeting of host APOBEC3H. Authors: Fumiaki Ito / Ana L Alvarez-Cabrera / Kyumin Kim / Z Hong Zhou / Xiaojiang S Chen / Abstract: 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. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 8fvi.cif.gz | 189.7 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb8fvi.ent.gz | 141.7 KB | Display | PDB format |
PDBx/mmJSON format | 8fvi.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8fvi_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 8fvi_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 8fvi_validation.xml.gz | 55.4 KB | Display | |
Data in CIF | 8fvi_validation.cif.gz | 79.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/fv/8fvi ftp://data.pdbj.org/pub/pdb/validation_reports/fv/8fvi | HTTPS FTP |
-Related structure data
Related structure data | 29488MC 8fvjC C: citing same article (ref.) M: map data used to model this data |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
-Protein , 6 types, 6 molecules 01Axyz
#1: Protein | Mass: 18643.814 Da / Num. of mol.: 1 / Fragment: UNP residues 1-157 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CBFB / Production host: Escherichia coli (E. coli) / References: UniProt: Q13951 |
---|---|
#2: Protein | Mass: 21160.451 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Strain: pNL4-3 / Gene: vif / Production host: Escherichia coli (E. coli) / References: UniProt: P12504 |
#3: Protein | Mass: 22103.410 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: APOBEC3H / Production host: Escherichia coli (E. coli) References: UniProt: Q6NTF7, single-stranded DNA cytosine deaminase |
#6: Protein | Mass: 36613.980 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CUL5 / Production host: Escherichia coli (E. coli) / References: UniProt: A0A2K5ZN28 |
#7: Protein | Mass: 11488.030 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ELOB, TCEB2 / Production host: Escherichia coli (E. coli) / References: UniProt: Q15370 |
#8: Protein | Mass: 10843.420 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ELOC, TCEB1 / Production host: Escherichia coli (E. coli) / References: UniProt: Q15369 |
-RNA chain , 2 types, 2 molecules BC
#4: RNA chain | Mass: 3039.740 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) |
---|---|
#5: RNA chain | Mass: 2917.895 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) |
-Non-polymers , 2 types, 3 molecules
#9: Chemical | #10: Water | ChemComp-HOH / | |
---|
-Details
Has ligand of interest | N |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Hetero-hexameric complex of HIV-1 Vif and human APOBEC3H, CBF-beta, ELOB, ELOC, and CUL5 Type: COMPLEX / Entity ID: #1-#8 / Source: MULTIPLE SOURCES | ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Molecular weight | Value: 0.12 MDa / Experimental value: NO | ||||||||||||||||
Source (natural) |
| ||||||||||||||||
Source (recombinant) | Organism: Escherichia coli (E. coli) | ||||||||||||||||
Buffer solution | pH: 7.5 | ||||||||||||||||
Specimen | Conc.: 0.15 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 165000 X / Nominal defocus max: 3000 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm |
Image recording | Average exposure time: 3.5 sec. / Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 14725 |
-Processing
Software | Name: PHENIX / Version: 1.20.1_4487: / Classification: refinement | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
EM software |
| ||||||||||||||||||||||||
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Particle selection | Num. of particles selected: 3637921 | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.24 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 89986 / Num. of class averages: 1 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
|