[English] 日本語
Yorodumi
- PDB-9e9v: Structural Insights into HIV-1 Vif-Mediated Ubiquitination and De... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9e9v
TitleStructural Insights into HIV-1 Vif-Mediated Ubiquitination and Degradation of APOBEC3H
Components
  • Core-binding factor subunit beta
  • Elongin-B
  • Elongin-C
  • RNA (5'-R(P*CP*CP*CP*GP*GP*CP*A)-3')
  • RNA (5'-R(P*GP*CP*CP*GP*GP*G)-3')
  • Virion infectivity factor
  • single-stranded DNA cytosine deaminase
KeywordsVIRAL PROTEIN/RNA / 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 / target-directed miRNA degradation / elongin complex / RUNX1 regulates transcription of genes involved in differentiation of myeloid cells / Regulation of RUNX1 Expression and Activity / VCB complex / Cul5-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / RUNX1 regulates transcription of genes involved in WNT signaling / RUNX1 regulates estrogen receptor mediated transcription / negative regulation of viral genome replication / Cul2-RING ubiquitin ligase complex / RUNX2 regulates osteoblast differentiation / RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known / 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 / viral life cycle / cell maturation / RNA Polymerase II Pre-transcription Events / transcription corepressor binding / TP53 Regulates Transcription of DNA Repair Genes / transcription initiation at RNA polymerase II promoter / transcription elongation by RNA polymerase II / Regulation of RUNX3 expression and activity / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / Vif-mediated degradation of APOBEC3G / Inactivation of CSF3 (G-CSF) signaling / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Evasion by RSV of host interferon responses / virion component / Regulation of expression of SLITs and ROBOs / Transcriptional regulation of granulopoiesis / protein polyubiquitination / Regulation of RUNX2 expression and activity / osteoblast differentiation / 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-containing complex assembly / Estrogen-dependent gene expression / defense response to virus / sequence-specific DNA binding / protein-macromolecule adaptor activity / transcription by RNA polymerase II / ubiquitin-dependent protein catabolic process / host cell cytoplasm / transcription coactivator activity / protein ubiquitination / 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 / cytoplasm / cytosol
Similarity search - Function
APOBEC3H / APOBEC3H / 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 / APOBEC3H / 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. / Cytidine deaminase-like / Elongin-C / Elongin B / 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
Similarity search - Domain/homology
RNA / single-stranded DNA cytosine deaminase / Virion infectivity factor / Core-binding factor subunit beta / Elongin-C / Elongin-B
Similarity search - Component
Biological speciesPan troglodytes (chimpanzee)
Homo sapiens (human)
Human immunodeficiency virus 1
Escherichia coli BL21 (bacteria)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4 Å
AuthorsMatsuo, H. / Skorupka, K.A.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)R01 AI150478 United States
CitationJournal: 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.
History
DepositionNov 8, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 11, 2026Provider: repository / Type: Initial release
Revision 1.0Mar 11, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Mar 11, 2026Data content type: FSC / Data content type: FSC / Provider: repository / Type: Initial release
Revision 1.0Mar 11, 2026Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Mar 11, 2026Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Mar 11, 2026Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Mar 11, 2026Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: single-stranded DNA cytosine deaminase
B: single-stranded DNA cytosine deaminase
D: RNA (5'-R(P*CP*CP*CP*GP*GP*CP*A)-3')
C: RNA (5'-R(P*GP*CP*CP*GP*GP*G)-3')
E: single-stranded DNA cytosine deaminase
H: RNA (5'-R(P*CP*CP*CP*GP*GP*CP*A)-3')
G: RNA (5'-R(P*GP*CP*CP*GP*GP*G)-3')
n: Elongin-C
m: Elongin-B
p: Virion infectivity factor
o: Core-binding factor subunit beta
t: Virion infectivity factor
s: Core-binding factor subunit beta
hetero molecules


Theoretical massNumber of molelcules
Total (without water)182,50317
Polymers182,24113
Non-polymers2624
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

-
Components

-
Protein , 5 types, 9 molecules ABEnmptos

#1: Protein single-stranded DNA cytosine deaminase


Mass: 21768.180 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Pan troglodytes (chimpanzee) / Gene: APOBEC3H / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: B7T0U6, single-stranded DNA cytosine deaminase
#4: Protein Elongin-C / EloC / Elongin 15 kDa subunit / RNA polymerase II transcription factor SIII subunit C / SIII p15 / ...EloC / Elongin 15 kDa subunit / RNA polymerase II transcription factor SIII subunit C / SIII p15 / Transcription elongation factor B polypeptide 1


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 BL21(DE3) (bacteria) / References: UniProt: Q15369
#5: Protein Elongin-B / EloB / Elongin 18 kDa subunit / RNA polymerase II transcription factor SIII subunit B / SIII p18 / ...EloB / Elongin 18 kDa subunit / RNA polymerase II transcription factor SIII subunit B / SIII p18 / Transcription elongation factor B polypeptide 2


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 BL21(DE3) (bacteria) / References: UniProt: Q15370
#6: Protein Virion infectivity factor / Vif / SOR protein


Mass: 20982.240 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Human immunodeficiency virus 1 / Gene: vif / Variant: NL4-3 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P12504
#7: Protein Core-binding factor subunit beta / CBF-beta / Polyomavirus enhancer-binding protein 2 beta subunit / PEA2-beta / PEBP2-beta / SL3-3 ...CBF-beta / Polyomavirus enhancer-binding protein 2 beta subunit / PEA2-beta / PEBP2-beta / SL3-3 enhancer factor 1 subunit beta / SL3/AKV core-binding factor beta subunit


Mass: 20272.629 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CBFB / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q13951

-
RNA chain , 2 types, 4 molecules DHCG

#2: RNA chain RNA (5'-R(P*CP*CP*CP*GP*GP*CP*A)-3')


Mass: 3159.965 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Escherichia coli BL21(DE3) (bacteria)
#3: RNA chain RNA (5'-R(P*GP*CP*CP*GP*GP*G)-3')


Mass: 2887.767 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Escherichia coli BL21(DE3) (bacteria)

-
Non-polymers , 1 types, 4 molecules

#8: Chemical
ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: Zn

-
Details

Has ligand of interestN
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: Ternary complex of APOBEC3H and Vif of HIV-1 / Type: COMPLEX / Entity ID: #2-#3 / Source: MULTIPLE SOURCES
Source (natural)Organism: Pan troglodytes (chimpanzee)
Source (recombinant)Organism: Escherichia coli (E. coli) / Strain: BL21 (DE3)
Buffer solutionpH: 7.4
Buffer component
IDConc.NameFormulaBuffer-ID
125 mMHEPESC8H18N2O4S1
2200 mMsodium chlorideNaCl1
31 mMTCEP1
40.25 %glycerol1
SpecimenConc.: 0.3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 281 K

-
Electron microscopy imaging

Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company
MicroscopyModel: FEI TECNAI ARCTICA
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2200 nm / Nominal defocus min: 800 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm / Alignment procedure: COMA FREE
Specimen holderCryogen: NITROGEN
Image recordingElectron dose: 45 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 3 / Num. of real images: 44142

-
Processing

EM software
IDNameVersionCategory
2EPU4image acquisition
7UCSF Chimera1.6model fitting
9PHENIX1.21-5207model refinement
13cryoSPARC4.4.13D reconstruction
CTF correctionType: PHASE FLIPPING ONLY
SymmetryPoint symmetry: C1 (asymmetric)
3D reconstructionResolution: 4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 215818 / Symmetry type: POINT
Atomic model buildingB value: 135 / Protocol: RIGID BODY FIT
Atomic model building

3D fitting-ID: 1 / Source name: PDB / Type: experimental model

IDPDB-IDPdb chain-IDAccession codeChain-IDInitial refinement model-ID
14N9Z

4n9z

m4N9Zm1
24N9Z

4n9z

n4N9Zn1
34N9Z

4n9z

o4N9Zo1
44N9Z

4n9z

p4N9Zp1
55Z98

5z98

A5Z98A2
65Z98

5z98

B5Z98B2
75Z98

5z98

C5Z98C2
85Z98

5z98

D5Z98D2
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00111252
ELECTRON MICROSCOPYf_angle_d0.40415312
ELECTRON MICROSCOPYf_dihedral_angle_d12.5914444
ELECTRON MICROSCOPYf_chiral_restr0.0361631
ELECTRON MICROSCOPYf_plane_restr0.0141857

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more