+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-9380 | |||||||||
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Title | cryoEM structure of the truncated HIV-1 Vif/CBFbeta/A3F complex | |||||||||
Map data | ||||||||||
Sample |
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Keywords | Human antiviral restriction factor / HIV viral protein / ANTIVIRAL PROTEIN | |||||||||
Function / homology | Function and homology information RUNX3 regulates RUNX1-mediated transcription / apolipoprotein B mRNA editing enzyme complex / 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 / base conversion or substitution editing ...RUNX3 regulates RUNX1-mediated transcription / apolipoprotein B mRNA editing enzyme complex / 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 / base conversion or substitution editing / single-stranded DNA cytosine deaminase / negative regulation of CD4-positive, alpha-beta T cell differentiation / DNA cytosine deamination / lymphocyte differentiation / cytidine to uridine editing / clearance of foreign intracellular DNA / cytidine deaminase activity / negative regulation of viral process / 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 / positive regulation of gene expression via chromosomal CpG island demethylation / RUNX1 regulates transcription of genes involved in differentiation of keratinocytes / myeloid cell differentiation / RUNX3 Regulates Immune Response and Cell Migration / definitive hemopoiesis / RUNX1 regulates transcription of genes involved in differentiation of myeloid cells / Regulation of RUNX1 Expression and Activity / negative regulation of viral genome replication / 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 / RUNX3 regulates p14-ARF / positive regulation of defense response to virus by host / cell maturation / viral life cycle / virion component / P-body / Regulation of RUNX3 expression and activity / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / osteoblast differentiation / Transcriptional regulation of granulopoiesis / protein polyubiquitination / Regulation of RUNX2 expression and activity / RUNX1 regulates transcription of genes involved in differentiation of HSCs / defense response to virus / Estrogen-dependent gene expression / sequence-specific DNA binding / host cell cytoplasm / transcription by RNA polymerase II / transcription coactivator activity / ribonucleoprotein complex / innate immune response / 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 / identical protein binding / membrane / nucleus / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | Human immunodeficiency virus 1 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||
Authors | Hu Y / Xiong Y | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Nat Struct Mol Biol / Year: 2019 Title: Structural basis of antagonism of human APOBEC3F by HIV-1 Vif. Authors: Yingxia Hu / Belete A Desimmie / Henry C Nguyen / Samantha J Ziegler / Tat Cheung Cheng / John Chen / Jia Wang / Hongwei Wang / Kai Zhang / Vinay K Pathak / Yong Xiong / Abstract: HIV-1 virion infectivity factor (Vif) promotes degradation of the antiviral APOBEC3 (A3) proteins through the host ubiquitin-proteasome pathway to enable viral immune evasion. Disrupting Vif-A3 ...HIV-1 virion infectivity factor (Vif) promotes degradation of the antiviral APOBEC3 (A3) proteins through the host ubiquitin-proteasome pathway to enable viral immune evasion. Disrupting Vif-A3 interactions to reinstate the A3-catalyzed suppression of human immunodeficiency virus type 1 (HIV-1) replication is a potential approach for antiviral therapeutics. However, the molecular mechanisms by which Vif recognizes A3 proteins remain elusive. Here we report a cryo-EM structure of the Vif-targeted C-terminal domain of human A3F in complex with HIV-1 Vif and the cellular cofactor core-binding factor beta (CBFβ) at 3.9-Å resolution. The structure shows that Vif and CBFβ form a platform to recruit A3F, revealing a direct A3F-recruiting role of CBFβ beyond Vif stabilization, and captures multiple independent A3F-Vif interfaces. Together with our biochemical and cellular studies, our structural findings establish the molecular determinants that are critical for Vif-mediated neutralization of A3F and provide a comprehensive framework of how HIV-1 Vif hijacks the host protein degradation machinery to counteract viral restriction by A3F. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_9380.map.gz | 4.6 MB | EMDB map data format | |
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Header (meta data) | emd-9380-v30.xml emd-9380.xml | 14.2 KB 14.2 KB | Display Display | EMDB header |
Images | emd_9380.png | 135.3 KB | ||
Filedesc metadata | emd-9380.cif.gz | 6.1 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-9380 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-9380 | HTTPS FTP |
-Validation report
Summary document | emd_9380_validation.pdf.gz | 379.4 KB | Display | EMDB validaton report |
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Full document | emd_9380_full_validation.pdf.gz | 379 KB | Display | |
Data in XML | emd_9380_validation.xml.gz | 5.9 KB | Display | |
Data in CIF | emd_9380_validation.cif.gz | 6.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9380 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9380 | HTTPS FTP |
-Related structure data
Related structure data | 6nilMC 9381C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_9380.map.gz / Format: CCP4 / Size: 42.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.05 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : truncated Vif/CBFbeta/A3Fctd complex
Entire | Name: truncated Vif/CBFbeta/A3Fctd complex |
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Components |
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-Supramolecule #1: truncated Vif/CBFbeta/A3Fctd complex
Supramolecule | Name: truncated Vif/CBFbeta/A3Fctd complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: Human immunodeficiency virus 1 |
Molecular weight | Theoretical: 17 KDa |
-Supramolecule #2: 6xHis tagged hA3Fctd-40aa-hCBFbeta fusion
Supramolecule | Name: 6xHis tagged hA3Fctd-40aa-hCBFbeta fusion / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#2 Details: The N-terminus of human CBFbeta is fused to human A3Fctd through a 40 amino acid linker:GVDGSDEASELACPTPKEDGLAQQQTQLNLRSQATGSGSG |
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Source (natural) | Organism: Homo sapiens (human) |
-Supramolecule #3: alpha domain truncated HIV-1 Vif
Supramolecule | Name: alpha domain truncated HIV-1 Vif / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3 |
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Source (natural) | Organism: Human immunodeficiency virus 1 |
-Macromolecule #1: DNA dC->dU-editing enzyme APOBEC-3F
Macromolecule | Name: DNA dC->dU-editing enzyme APOBEC-3F / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO / EC number: single-stranded DNA cytosine deaminase |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 24.433271 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MGSSHHHHHH SQDPNSMGKE ILRNPMEAMD PHIFYFHFKN LRKAYGRNES WLCFTMEVVK HHSPVSWKRG VFRNQVDPET GRHAERCFL SWFCDDILSP NTNYEVTWYT SWSPCPECAG EVAEFLARHS NVNLTIKTAR LYYFKDTDAA EGLRSLSQEG A SVEIMGYK ...String: MGSSHHHHHH SQDPNSMGKE ILRNPMEAMD PHIFYFHFKN LRKAYGRNES WLCFTMEVVK HHSPVSWKRG VFRNQVDPET GRHAERCFL SWFCDDILSP NTNYEVTWYT SWSPCPECAG EVAEFLARHS NVNLTIKTAR LYYFKDTDAA EGLRSLSQEG A SVEIMGYK DFKYCWENFV YNDDEPFKPW DGLDYNFLDL DSKLQEILE UniProtKB: DNA dC->dU-editing enzyme APOBEC-3F |
-Macromolecule #2: Core-binding factor subunit beta
Macromolecule | Name: Core-binding factor subunit beta / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 17.851043 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MPRVVPDQRS KFENEEFFRK LSRECEIKYT GFRDRPHEER QARFQNACRD GRSEIAFVAT GTNLSLQFFP ASWQGEQRQT PSREYVDLE REAGKVYLKA PMILNGVCVI WKGWIDLQRL DGMGCLEFDE ERAQQEDALA QQAFEEARRR TR UniProtKB: Core-binding factor subunit beta |
-Macromolecule #3: Virion infectivity factor
Macromolecule | Name: Virion infectivity factor / type: protein_or_peptide / ID: 3 Details: Residues 114-157 was replaced with a 6 amino acid linker (EASEGS). The C-terminal residues 177-192 were deleted. Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Human immunodeficiency virus 1 |
Molecular weight | Theoretical: 16.736102 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MENRWQVMIV WQVDRMRINT WKRLVKHHMY ISRKAKDWFY RHHYESTNPK ISSEVHIPLG DAKLVITTYW GLHTGERDWH LGQGVSIEW RKKRYSTQVD PDLADQLIHL HYFDEASEGS QIKPPLPSVR KLTEDRWNK UniProtKB: Virion infectivity factor, Virion infectivity factor |
-Macromolecule #4: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 4 / Number of copies: 4 / Formula: ZN |
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Molecular weight | Theoretical: 65.409 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
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Grid | Details: unspecified |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 56.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: INSILICO MODEL |
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Final reconstruction | Applied symmetry - Point group: D2 (2x2 fold dihedral) / Resolution.type: BY AUTHOR / Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 337256 |
Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |