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- PDB-9zy1: Cryo-EM structure of the dimeric HIV-2 Vif-human APOBEC3H-CBFbeta... -

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Basic information

Entry
Database: PDB / ID: 9zy1
TitleCryo-EM structure of the dimeric HIV-2 Vif-human APOBEC3H-CBFbeta complex
Components
  • Core-binding factor subunit beta
  • RNA (5'-R(P*AP*AP*AP*AP*AP*AP*AP*A)-3')
  • RNA (5'-R(P*UP*UP*UP*UP*UP*UP*UP*U)-3')
  • Single-stranded DNA cytosine deaminase
  • Virion infectivity factor
KeywordsANTIVIRAL PROTEIN/RNA / HIV-2 / Vif / APOBEC3H / Antagonism / Ubiquitination / ANTIVIRAL PROTEIN / ANTIVIRAL 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 / core-binding factor complex / RUNX2 regulates bone development / 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 / core-binding factor complex / RUNX2 regulates bone development / 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 / cytidine deaminase activity / RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs) / lymphocyte differentiation / RUNX2 regulates genes involved in cell migration / Transcriptional regulation by RUNX2 / RUNX1 regulates transcription of genes involved in differentiation of keratinocytes / RUNX2 regulates genes involved in differentiation of myeloid cells / myeloid cell differentiation / transposable element silencing / 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 / 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 / cell maturation / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / Regulation of RUNX3 expression and activity / Transcriptional regulation of granulopoiesis / osteoblast differentiation / protein polyubiquitination / Regulation of RUNX2 expression and activity / RUNX1 regulates transcription of genes involved in differentiation of HSCs / transcription by RNA polymerase II / Estrogen-dependent gene expression / sequence-specific DNA binding / defense response to virus / transcription coactivator activity / regulation of transcription by RNA polymerase II / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / zinc ion binding / nucleoplasm / membrane / cytoplasm
Similarity search - Function
APOBEC3H / APOBEC3H / 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 / Core-binding factor subunit beta / :
Similarity search - Component
Biological speciesHuman immunodeficiency virus 2
Homo sapiens (human)
synthetic construct (others)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å
AuthorsNiu, Y. / Lilly, M. / Ronayne, E.K. / Emerman, M. / Chesarino, N.M. / Gross, J.D.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)U54AI170792 United States
CitationJournal: Nat Commun / Year: 2026
Title: The structural mechanism of HIV-2 Vif antagonism of human APOBEC3H.
Authors: Yange Niu / Michelle Lilly / Estelle K Ronayne / Michael Emerman / Nicholas M Chesarino / John D Gross /
Abstract: Human APOBEC3 (A3) proteins restrict retrovirus infection by inducing hypermutations in viral cDNA. To counteract this restriction, lentiviruses, such as HIV-1 and HIV-2 encode the viral infectivity ...Human APOBEC3 (A3) proteins restrict retrovirus infection by inducing hypermutations in viral cDNA. To counteract this restriction, lentiviruses, such as HIV-1 and HIV-2 encode the viral infectivity factor (Vif), which hijacks a host Cullin-RING E3 ubiquitin ligase complex to target A3 proteins for proteasomal degradation. Here, we present the cryo-EM structure of HIV-2 Vif in complex with human A3H and CBFβ. The structure reveals that A3H forms a dimer mediated by dsRNA where each A3H monomer directly interacts with an HIV-2 Vif and the host protein CBFβ. Both HIV-2 Vif-A3H and CBFβ-A3H interfaces are critical for A3H degradation. Notably, however, the HIV-2 Vif-A3H interface is entirely distinct from the previously determined cryo-EM structure of the HIV-1 Vif and A3H complex. These findings suggest that HIV-1 and HIV-2 Vif, which are the result of distinct cross-species transmissions from species with different A3H characteristics, have followed separate evolutionary trajectories to counteract human A3H.
History
DepositionJan 5, 2026Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 15, 2026Provider: repository / Type: Initial release
Revision 1.0Jul 15, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Jul 15, 2026Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jul 15, 2026Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jul 15, 2026Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Jul 15, 2026Data content type: Mask / Part number: 1 / Data content type: Mask / Provider: repository / Type: Initial release
Revision 1.0Jul 15, 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
1: Virion infectivity factor
2: Core-binding factor subunit beta
3: Single-stranded DNA cytosine deaminase
A: Virion infectivity factor
B: Core-binding factor subunit beta
C: Single-stranded DNA cytosine deaminase
D: RNA (5'-R(P*UP*UP*UP*UP*UP*UP*UP*U)-3')
E: RNA (5'-R(P*AP*AP*AP*AP*AP*AP*AP*A)-3')
hetero molecules


Theoretical massNumber of molelcules
Total (without water)141,82410
Polymers141,6938
Non-polymers1312
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

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Protein , 3 types, 6 molecules 1A2B3C

#1: Protein Virion infectivity factor


Mass: 25044.865 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Human immunodeficiency virus 2 / Gene: vif / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q9YTT9
#2: 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: 21542.188 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CBFB / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q13951
#3: Protein Single-stranded DNA cytosine deaminase


Mass: 21763.137 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: APOBEC3H / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: B7TQM6, single-stranded DNA cytosine deaminase

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RNA chain , 2 types, 2 molecules DE

#4: RNA chain RNA (5'-R(P*UP*UP*UP*UP*UP*UP*UP*U)-3')


Mass: 2404.369 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) synthetic construct (others) / Production host: Spodoptera frugiperda (fall armyworm)
#5: RNA chain RNA (5'-R(P*AP*AP*AP*AP*AP*AP*AP*A)-3')


Mass: 2588.689 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) synthetic construct (others) / Production host: Spodoptera frugiperda (fall armyworm)

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Non-polymers , 1 types, 2 molecules

#6: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn / Feature type: SUBJECT OF INVESTIGATION

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Details

Has ligand of interestY
Has protein modificationN

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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: HIV-2 Vif in complex with human APOBEC3H and CBFbeta / Type: COMPLEX / Entity ID: #1-#5 / Source: MULTIPLE SOURCES
Molecular weightValue: 0.13 MDa / Experimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Spodoptera frugiperda (fall armyworm)
Buffer solutionpH: 7.2
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 1200 nm
Image recordingElectron dose: 47.7 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

EM software
IDNameCategory
1cryoSPARCparticle selection
13cryoSPARC3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 1257210 / Symmetry type: POINT

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