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Yorodumi- EMDB-27032: Cryo-EM structure of human APOBEC3G/HIV-1 Vif/CBFbeta/ELOB/ELOC m... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-27032 | |||||||||
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Title | Cryo-EM structure of human APOBEC3G/HIV-1 Vif/CBFbeta/ELOB/ELOC monomeric complex | |||||||||
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Keywords | Viral protein / RNA binding protein / Complex / Ubiquitin E3 ligase / VIRAL PROTEIN-IMMUNE SYSTEM-RNA complex | |||||||||
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 / dCTP deaminase activity / cytidine deamination / 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 ...RUNX3 regulates RUNX1-mediated transcription / apolipoprotein B mRNA editing enzyme complex / RUNX1 regulates transcription of genes involved in BCR signaling / dCTP deaminase activity / cytidine deamination / 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 / cytidine deaminase activity / RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs) / negative regulation of viral process / 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 / retrotransposon 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 / Cul2-RING ubiquitin ligase complex / 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 / APOBEC3G mediated resistance to HIV-1 infection / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / RUNX3 regulates p14-ARF / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / 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 / positive regulation of defense response to virus by host / viral life cycle / RNA Polymerase II Pre-transcription Events / transcription corepressor binding / virion component / transcription elongation by RNA polymerase II / transcription initiation at RNA polymerase II promoter / TP53 Regulates Transcription of DNA Repair Genes / Vif-mediated degradation of APOBEC3G / Regulation of RUNX3 expression and activity / P-body / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Inactivation of CSF3 (G-CSF) signaling / 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 / protein-macromolecule adaptor activity / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Neddylation / 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 / ribonucleoprotein complex / 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 / identical protein binding Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Human immunodeficiency virus 1 / Spodoptera frugiperda (fall armyworm) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.7 Å | |||||||||
Authors | Li Y / Langley C / Azumaya CM / Echeverria I / Chesarino NM / Emerman M / Cheng Y / Gross JD | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Nature / Year: 2023 Title: The structural basis for HIV-1 Vif antagonism of human APOBEC3G. Authors: Yen-Li Li / Caroline A Langley / Caleigh M Azumaya / Ignacia Echeverria / Nicholas M Chesarino / Michael Emerman / Yifan Cheng / John D Gross / Abstract: The APOBEC3 (A3) proteins are host antiviral cellular proteins that hypermutate the viral genome of diverse viral families. In retroviruses, this process requires A3 packaging into viral particles. ...The APOBEC3 (A3) proteins are host antiviral cellular proteins that hypermutate the viral genome of diverse viral families. In retroviruses, this process requires A3 packaging into viral particles. The lentiviruses encode a protein, Vif, that antagonizes A3 family members by targeting them for degradation. Diversification of A3 allows host escape from Vif whereas adaptations in Vif enable cross-species transmission of primate lentiviruses. How this 'molecular arms race' plays out at the structural level is unknown. Here, we report the cryogenic electron microscopy structure of human APOBEC3G (A3G) bound to HIV-1 Vif, and the hijacked cellular proteins that promote ubiquitin-mediated proteolysis. A small surface explains the molecular arms race, including a cross-species transmission event that led to the birth of HIV-1. Unexpectedly, we find that RNA is a molecular glue for the Vif-A3G interaction, enabling Vif to repress A3G by ubiquitin-dependent and -independent mechanisms. Our results suggest a model in which Vif antagonizes A3G by intercepting it in its most dangerous form for the virus-when bound to RNA and on the pathway to packaging-to prevent viral restriction. By engaging essential surfaces required for restriction, Vif exploits a vulnerability in A3G, suggesting a general mechanism by which RNA binding helps to position key residues necessary for viral antagonism of a host antiviral gene. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_27032.map.gz | 83.1 MB | EMDB map data format | |
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Header (meta data) | emd-27032-v30.xml emd-27032.xml | 27.8 KB 27.8 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_27032_fsc.xml | 12.5 KB | Display | FSC data file |
Images | emd_27032.png | 61.6 KB | ||
Masks | emd_27032_msk_1.map | 166.4 MB | Mask map | |
Filedesc metadata | emd-27032.cif.gz | 7 KB | ||
Others | emd_27032_additional_1.map.gz emd_27032_additional_2.map.gz emd_27032_additional_3.map.gz emd_27032_half_map_1.map.gz emd_27032_half_map_2.map.gz | 18.1 MB 82.6 MB 142.7 MB 154.3 MB 154.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-27032 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-27032 | HTTPS FTP |
-Validation report
Summary document | emd_27032_validation.pdf.gz | 804 KB | Display | EMDB validaton report |
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Full document | emd_27032_full_validation.pdf.gz | 803.5 KB | Display | |
Data in XML | emd_27032_validation.xml.gz | 20.2 KB | Display | |
Data in CIF | emd_27032_validation.cif.gz | 26.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27032 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27032 | HTTPS FTP |
-Related structure data
Related structure data | 8cx0MC 8cx1C 8cx2C C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_27032.map.gz / Format: CCP4 / Size: 166.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.835 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_27032_msk_1.map | ||||||||||||
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-Additional map: Density-modified map
File | emd_27032_additional_1.map | ||||||||||||
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Annotation | Density-modified map | ||||||||||||
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-Additional map: Raw Map before signal-subtraction focused refinement
File | emd_27032_additional_2.map | ||||||||||||
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Annotation | Raw Map before signal-subtraction focused refinement | ||||||||||||
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-Additional map: Sharpened map processed by DeepEMhancer
File | emd_27032_additional_3.map | ||||||||||||
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Annotation | Sharpened map processed by DeepEMhancer | ||||||||||||
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-Half map: #2
File | emd_27032_half_map_1.map | ||||||||||||
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-Half map: #1
File | emd_27032_half_map_2.map | ||||||||||||
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Density Histograms |
-Sample components
-Entire : HIV-1 Vif-E3 ligase substrate receptor (VCBC) in complex with hum...
Entire | Name: HIV-1 Vif-E3 ligase substrate receptor (VCBC) in complex with human APOBEC3G and RNA |
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Components |
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-Supramolecule #1: HIV-1 Vif-E3 ligase substrate receptor (VCBC) in complex with hum...
Supramolecule | Name: HIV-1 Vif-E3 ligase substrate receptor (VCBC) in complex with human APOBEC3G and RNA type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#6 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: DNA dC->dU-editing enzyme APOBEC-3G
Macromolecule | Name: DNA dC->dU-editing enzyme APOBEC-3G / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: single-stranded DNA cytosine deaminase |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 50.034598 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MKPHFRNTVE RMYRDTFSYN FYNRPILSRR NTVWLCYEVK TKGPSRPPLD AKIFRGQVYS ELKYHPEMRF FHWFSKWRKL HRDQEYEVT WYISWSPCTK CTRDMATFLA EDPKVTLTIF VARLYYFWDP DYQEALRSLC QKRDGPRATM KIMNYDEFQH C WSKFVYSQ ...String: MKPHFRNTVE RMYRDTFSYN FYNRPILSRR NTVWLCYEVK TKGPSRPPLD AKIFRGQVYS ELKYHPEMRF FHWFSKWRKL HRDQEYEVT WYISWSPCTK CTRDMATFLA EDPKVTLTIF VARLYYFWDP DYQEALRSLC QKRDGPRATM KIMNYDEFQH C WSKFVYSQ RELFEPWNNL PKYYILLHIM LGEILRHSMD PPTFTFNFNN EPWVRGRHET YLCYEVERMH NDTWVLLNQR RG FLCNQAP HKHGFLEGRH AELCFLDVIP FWKLDLDQDY RVTCFTSWSP CFSCAQEMAK FISKNKHVSL CIFTARIYDD QGR CQEGLR TLAEAGAKIS IMTYSEFKHC WDTFVDHQGC PFQPWDGLDE HSQDLSGRLR AILQNQENGS SLEGGGGWSH PQFE KGGGS GGGSGGGSWS HPQFEK UniProtKB: DNA dC->dU-editing enzyme APOBEC-3G |
-Macromolecule #2: Virion infectivity factor
Macromolecule | Name: Virion infectivity factor / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Human immunodeficiency virus 1 |
Molecular weight | Theoretical: 22.556002 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MENRWQVMIV WQVDRMRIRT WKSLVKHHMY VSGKARGWFY RHHYESPHPR ISSEVHIPLG DARLVITTYW GLHTGERDWH LGQGVSIEW RKKRYSTQVD PELADQLIHL YYFDCFSDSA IRKALLGHIV SPRCEYQAGH NKVGSLQYLA LAALITPKKI K PPLPSVTK ...String: MENRWQVMIV WQVDRMRIRT WKSLVKHHMY VSGKARGWFY RHHYESPHPR ISSEVHIPLG DARLVITTYW GLHTGERDWH LGQGVSIEW RKKRYSTQVD PELADQLIHL YYFDCFSDSA IRKALLGHIV SPRCEYQAGH NKVGSLQYLA LAALITPKKI K PPLPSVTK LTEDRWNKPQ KTKGHRGSHT MNGH UniProtKB: Virion infectivity factor |
-Macromolecule #3: Core-binding factor subunit beta
Macromolecule | Name: Core-binding factor subunit beta / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 21.542188 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MPRVVPDQRS KFENEEFFRK LSRECEIKYT GFRDRPHEER QARFQNACRD GRSEIAFVAT GTNLSLQFFP ASWQGEQRQT PSREYVDLE REAGKVYLKA PMILNGVCVI WKGWIDLQRL DGMGCLEFDE ERAQQEDALA QQAFEEARRR TREFEDRDRS H REEMEVRV SQLLAVTGKK TTRP UniProtKB: Core-binding factor subunit beta |
-Macromolecule #4: Elongin-B
Macromolecule | Name: Elongin-B / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 13.147781 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MDVFLMIRRH KTTIFTDAKE SSTVFELKRI VEGILKRPPD EQRLYKDDQL LDDGKTLGEC GFTSQTARPQ APATVGLAFR ADDTFEALC IEPFSSPPEL PDVMKPQDSG SSANEQAVQ UniProtKB: Elongin-B |
-Macromolecule #5: Elongin-C
Macromolecule | Name: Elongin-C / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 12.485135 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MDGEEKTYGG CEGPDAMYVK LISSDGHEFI VKREHALTSG TIKAMLSGPG QFAENETNEV NFREIPSHVL SKVCMYFTYK VRYTNSSTE IPEFPIAPEI ALELLMAANF LDC UniProtKB: Elongin-C |
-Macromolecule #6: RNA (5'-R(P*AP*AP*AP*AP*AP*AP*AP*A)-3')
Macromolecule | Name: RNA (5'-R(P*AP*AP*AP*AP*AP*AP*AP*A)-3') / type: rna / ID: 6 / Number of copies: 1 |
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Source (natural) | Organism: Spodoptera frugiperda (fall armyworm) |
Molecular weight | Theoretical: 2.588689 KDa |
Sequence | String: AAAAAAAA |
-Macromolecule #7: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 7 / Number of copies: 3 / 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
Concentration | 0.46 mg/mL |
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Buffer | pH: 7 |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 68.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 105000 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |