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- PDB-9e93: Structural Insights into HIV-1 Vif-Mediated Ubiquitination and De... -

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Basic information

Entry
Database: PDB / ID: 9.0E+93
TitleStructural Insights into HIV-1 Vif-Mediated Ubiquitination and Degradation of APOBEC3H
Components
  • Core-binding factor subunit beta
  • RNA (5'-R(*AP*UP*AP*CP*CP*CP*GP*GP*CP*A)-3')
  • RNA (5'-R(P*UP*GP*CP*CP*GP*GP*GP*UP*A)-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 / RUNX1 regulates transcription of genes involved in differentiation of myeloid cells / Regulation of RUNX1 Expression and Activity / RUNX1 regulates transcription of genes involved in WNT signaling / RUNX1 regulates estrogen receptor mediated transcription / negative regulation of viral genome replication / RUNX2 regulates osteoblast differentiation / RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known / RUNX3 regulates p14-ARF / viral life cycle / cell maturation / Regulation of RUNX3 expression and activity / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / virion component / Transcriptional regulation of granulopoiesis / protein polyubiquitination / Regulation of RUNX2 expression and activity / osteoblast differentiation / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Estrogen-dependent gene expression / defense response to virus / sequence-specific DNA binding / transcription by RNA polymerase II / host cell cytoplasm / transcription coactivator activity / 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
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
Similarity search - Domain/homology
RNA / single-stranded DNA cytosine deaminase / Virion infectivity factor / Core-binding factor subunit beta
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: 3.58 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 7, 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

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

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


Theoretical massNumber of molelcules
Total (without water)138,69114
Polymers138,43010
Non-polymers2624
Water00
1


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

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Components

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RNA chain , 2 types, 4 molecules CGDH

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


Mass: 2887.767 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Escherichia coli BL21(DE3) (bacteria)
#2: RNA chain RNA (5'-R(*AP*UP*AP*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)

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Protein , 3 types, 6 molecules AEospt

#3: Protein single-stranded DNA cytosine deaminase


Mass: 21912.309 Da / Num. of mol.: 2
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 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 (E. coli) / References: UniProt: Q13951
#5: 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 / Strain: NL3-4 / Gene: vif / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P12504

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Non-polymers , 1 types, 4 molecules

#6: Chemical
ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: Zn / Feature type: SUBJECT OF INVESTIGATION

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Details

Has ligand of interestY
Has protein modificationY

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Experimental details

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Experiment

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

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Sample preparation

ComponentName: Ternary complex of APOBEC3H and Vif of HIV-1 / Type: COMPLEX / Entity ID: #1-#2, #4-#5 / 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
Specimen supportDetails: 20 mA / Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R0.6/1
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 281 K

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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

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Processing

EM software
IDNameVersionCategory
2EPU4image acquisition
7UCSF Chimera1.6model fitting
12cryoSPARC4.4.13D reconstruction
13PHENIX1.21-5207model refinement
CTF correctionType: PHASE FLIPPING ONLY
SymmetryPoint symmetry: C2 (2 fold cyclic)
3D reconstructionResolution: 3.58 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 201593 / 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_d0.0029049
ELECTRON MICROSCOPYf_angle_d0.39712368
ELECTRON MICROSCOPYf_dihedral_angle_d13.6673640
ELECTRON MICROSCOPYf_chiral_restr0.0351319
ELECTRON MICROSCOPYf_plane_restr0.0071466

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