[English] 日本語
Yorodumi
- EMDB-54482: MVV CSC intasome in complex with LEDGF -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-54482
TitleMVV CSC intasome in complex with LEDGF
Map dataMap filtered using deepEMhancaer for display
Sample
  • Complex: MVV CSC intasome in complex with LEDGF
    • Protein or peptide: Gag-Pol polyprotein
    • DNA: EV306
    • DNA: EV272
    • Protein or peptide: PC4 and SFRS1-interacting protein
  • Ligand: ZINC ION
Keywordsintegrase / LEDGF / p75 / MVV / DNA / VIRAL PROTEIN
Function / homology
Function and homology information


dUTP diphosphatase / dUTP diphosphatase activity / nucleotide metabolic process / Integration of viral DNA into host genomic DNA / Autointegration results in viral DNA circles / ribonuclease H / Hydrolases; Acting on peptide bonds (peptidases); Aspartic endopeptidases / supercoiled DNA binding / 2-LTR circle formation / Vpr-mediated nuclear import of PICs ...dUTP diphosphatase / dUTP diphosphatase activity / nucleotide metabolic process / Integration of viral DNA into host genomic DNA / Autointegration results in viral DNA circles / ribonuclease H / Hydrolases; Acting on peptide bonds (peptidases); Aspartic endopeptidases / supercoiled DNA binding / 2-LTR circle formation / Vpr-mediated nuclear import of PICs / Formation of WDR5-containing histone-modifying complexes / mRNA 5'-splice site recognition / Integration of provirus / APOBEC3G mediated resistance to HIV-1 infection / heterochromatin / nuclear periphery / exoribonuclease H / exoribonuclease H activity / DNA integration / euchromatin / viral genome integration into host DNA / establishment of integrated proviral latency / RNA-directed DNA polymerase / RNA-directed DNA polymerase activity / RNA-DNA hybrid ribonuclease activity / Transferases; Transferring phosphorus-containing groups; Nucleotidyltransferases / viral capsid / response to heat / DNA recombination / response to oxidative stress / DNA-directed DNA polymerase / DNA-binding transcription factor binding / aspartic-type endopeptidase activity / Hydrolases; Acting on ester bonds / DNA-directed DNA polymerase activity / transcription coactivator activity / chromatin remodeling / viral translational frameshifting / chromatin binding / symbiont entry into host cell / positive regulation of transcription by RNA polymerase II / proteolysis / DNA binding / RNA binding / zinc ion binding / nucleoplasm / nucleus / cytosol
Similarity search - Function
Lens epithelium-derived growth factor, integrase-binding domain / HIV integrase-binding domain superfamily / Lens epithelium-derived growth factor (LEDGF) / dUTPase-like / dUTPase / dUTPase, trimeric / dUTPase-like superfamily / TFIIS/LEDGF domain superfamily / gag protein p24 N-terminal domain / domain with conserved PWWP motif ...Lens epithelium-derived growth factor, integrase-binding domain / HIV integrase-binding domain superfamily / Lens epithelium-derived growth factor (LEDGF) / dUTPase-like / dUTPase / dUTPase, trimeric / dUTPase-like superfamily / TFIIS/LEDGF domain superfamily / gag protein p24 N-terminal domain / domain with conserved PWWP motif / PWWP domain / PWWP domain profile. / PWWP domain / Reverse transcriptase connection / Reverse transcriptase connection domain / Integrase Zinc binding domain / Zinc finger integrase-type profile. / Integrase, C-terminal domain superfamily, retroviral / Integrase, N-terminal zinc-binding domain / Integrase, C-terminal, retroviral / Integrase-like, N-terminal / Integrase DNA binding domain profile. / RNase H / Integrase core domain / Integrase, catalytic core / Integrase catalytic domain profile. / RNase H type-1 domain profile. / Ribonuclease H domain / Retroviral nucleocapsid Gag protein p24, C-terminal domain / Gag protein p24 C-terminal domain / Retropepsins / Retroviral aspartyl protease / Aspartyl protease, retroviral-type family profile. / Peptidase A2A, retrovirus, catalytic / Reverse transcriptase (RNA-dependent DNA polymerase) / Retrovirus capsid, C-terminal / Reverse transcriptase domain / Reverse transcriptase (RT) catalytic domain profile. / Retrovirus capsid, N-terminal / zinc finger / Zinc knuckle / Zinc finger, CCHC-type superfamily / Zinc finger, CCHC-type / Zinc finger CCHC-type profile. / Aspartic peptidase, active site / Eukaryotic and viral aspartyl proteases active site. / Aspartic peptidase domain superfamily / Ribonuclease H superfamily / Ribonuclease H-like superfamily / Reverse transcriptase/Diguanylate cyclase domain / DNA/RNA polymerase superfamily
Similarity search - Domain/homology
PC4 and SFRS1-interacting protein / Gag-Pol polyprotein
Similarity search - Component
Biological speciesVisna-maedi virus / Maedi visna virus (strain KV1772) / Homo sapiens (human) / DNA molecule (others)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.8 Å
AuthorsPunch EK / Hope J / Cherepanov P
Funding support United States, United Kingdom, 4 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)U54AI170791 United States
Wellcome TrustCC2058 United Kingdom
Medical Research Council (MRC, United Kingdom)CC2058 United Kingdom
Cancer Research UKCC2058 United Kingdom
CitationJournal: Nat Commun / Year: 2026
Title: Core nucleosomes are refractory to lentiviral DNA integration.
Authors: Joshua Hope / Emma Punch / Nicola J Cook / Matthew R Singer / Dhira Joshi / Parmit K Singh / Andrea Nans / Nathan P Sweeney / Willem Vanderlinden / Alan N Engelman / Peter Cherepanov /
Abstract: HIV-1 and other lentiviruses hijack the cellular chromatin-binding protein LEDGF/p75 to facilitate integration into active transcription units. However, the mechanism of chromatin engagement by ...HIV-1 and other lentiviruses hijack the cellular chromatin-binding protein LEDGF/p75 to facilitate integration into active transcription units. However, the mechanism of chromatin engagement by lentiviral intasomes and the structural role of LEDGF/p75 in this process remain poorly understood. To address these gaps, we studied the activities of native HIV-1 preintegration complexes and in vitro-assembled lentiviral intasomes in the presence of chromatinized target DNA. While LEDGF/p75 was both essential and minimally sufficient to enhance lentiviral integration into chromatin containing histone H3 trimethylated on Lys36, it unexpectedly facilitated integration outside of the nucleosome core particles. LEDGF/p75 additionally inhibited integration into unmodified chromatin in a dose-dependent manner, promoting integration into naked DNA. To explore the structural foundation for these activities, we imaged maedi-visna virus intasomes saturated with LEDGF/p75 before and after strand transfer by cryogenic electron microscopy. The structures revealed that the host factor alters the target DNA binding platform of the lentiviral intasome, imposing significant constraints on the path and configuration of target DNA to impede nucleosome engagement. Our results establish the preference of lentiviral intasomes for linker DNA regions within H3K36Me3-enriched chromatin and show that LEDGF/p75 plays a specific structural role at the viral-host target DNA interface.
History
DepositionJul 21, 2025-
Header (metadata) releaseJul 29, 2026-
Map releaseJul 29, 2026-
UpdateSep 30, 2026-
Current statusSep 30, 2026Processing site: PDBe / Status: Released

-
Structure visualization

Supplemental images

emd_54482.png

Downloads & links

-
Map

FileDownload / File: emd_54482.map.gz / Format: CCP4 / Size: 325 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationMap filtered using deepEMhancaer for display
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.95 Å/pix.
x 440 pix.
= 418. Å		0.95 Å/pix.
x 440 pix.
= 418. Å		0.95 Å/pix.
x 440 pix.
= 418. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.95 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.02
Minimum - Maximum-0.0018434692 - 1.802085
Average (Standard dev.)0.00095154956 (±0.02017557)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions440440440
Spacing440440440
CellA=B=C: 418.0 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Additional map: Locally filtered map used for real-space refinement.

Fileemd_54482_additional_1.map
AnnotationLocally filtered map used for real-space refinement.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: Half map 1

Fileemd_54482_half_map_1.map
AnnotationHalf map 1
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: Half map 2

Fileemd_54482_half_map_2.map
AnnotationHalf map 2
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : MVV CSC intasome in complex with LEDGF

EntireName: MVV CSC intasome in complex with LEDGF
Components
  • Complex: MVV CSC intasome in complex with LEDGF
    • Protein or peptide: Gag-Pol polyprotein
    • DNA: EV306
    • DNA: EV272
    • Protein or peptide: PC4 and SFRS1-interacting protein
  • Ligand: ZINC ION

-
Supramolecule #1: MVV CSC intasome in complex with LEDGF

SupramoleculeName: MVV CSC intasome in complex with LEDGF / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4
Details: Integrase and LEDGF were produced in E. coli. The complex was assembled in vitro.
Source (natural)Organism: Visna-maedi virus / Strain: KV1772
Molecular weightTheoretical: 902 KDa

-
Macromolecule #1: Gag-Pol polyprotein

MacromoleculeName: Gag-Pol polyprotein / type: protein_or_peptide / ID: 1 / Number of copies: 16 / Enantiomer: LEVO
Source (natural)Organism: Maedi visna virus (strain KV1772) / Strain: KV1772
Molecular weightTheoretical: 32.368826 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: WIENIPLAEE EHNKWHQDAV SLHLEFGIPR TAAEDIVQQC DVCQENKMPS TLRGSNKRGI DHWQVDYTHY EDKIILVWVE TNSGLIYAE RVKGETGQEF RVQTMKWYAM FAPKSLQSDN GPAFVAESTQ LLMKYLGIEH TTGIPWNPQS QALVERTHQT L KNTLEKLI ...String:
WIENIPLAEE EHNKWHQDAV SLHLEFGIPR TAAEDIVQQC DVCQENKMPS TLRGSNKRGI DHWQVDYTHY EDKIILVWVE TNSGLIYAE RVKGETGQEF RVQTMKWYAM FAPKSLQSDN GPAFVAESTQ LLMKYLGIEH TTGIPWNPQS QALVERTHQT L KNTLEKLI PMFNAFESAL AGTLITLNIK RKGGLGTSPM DIFIFNKEQQ RIQQQSKSKQ EKIRFCYYRT RKRGHPGEWQ GP TQVLWGG DGAIVVKDRG TDRYLVIANK DVKFIPPPKE IQKE

UniProtKB: Gag-Pol polyprotein

-
Macromolecule #4: PC4 and SFRS1-interacting protein

MacromoleculeName: PC4 and SFRS1-interacting protein / type: protein_or_peptide / ID: 4 / Number of copies: 12 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 60.224453 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: MTRDFKPGDL IFAKMKGYPH WPARVDEVPD GAVKPPTNKL PIFFFGTHET AFLGPKDIFP YSENKEKYGK PNKRKGFNEG LWEIDNNPK VKFSSQQAAT KQSNASSDVE VEEKETSVSK EDTDHEEKAS NEDVTKAVDI TTPKAARRGR KRKAEKQVET E EAGVVTTA ...String:
MTRDFKPGDL IFAKMKGYPH WPARVDEVPD GAVKPPTNKL PIFFFGTHET AFLGPKDIFP YSENKEKYGK PNKRKGFNEG LWEIDNNPK VKFSSQQAAT KQSNASSDVE VEEKETSVSK EDTDHEEKAS NEDVTKAVDI TTPKAARRGR KRKAEKQVET E EAGVVTTA TASVNLKVSP KRGRPAATEV KIPKPRGRPK MVKQPCPSES DIITEEDKSK KKGQEEKQPK KQPKKDEEGQ KE EDKPRKE PDKKEGKKEV ESKRKNLAKT GVTSTSDSEE EGDDQEGEKK RKGGRNFQTA HRRNMLKGQH EKEAADRKRK QEE QMETEQ QNKDEGKKPE VKKVEKKRET SMDSRLQRIH AEIKNSLKID NLDVNRCIEA LDELASLQVT MQQAQKHTEM ITTL KKIRR FKVSQVIMEK STMLYNKFKN MFLVGEGDSV ITQVLNKSLA EQRQHEEANK TKDQGKKGPN KKLEKEQTGS KTLNG GSDA QDGNQPQHNG ESNEDSKDNH EASTKKKPSS EERETEISLK DSTLDN

UniProtKB: PC4 and SFRS1-interacting protein

-
Macromolecule #2: EV306

MacromoleculeName: EV306 / type: dna / ID: 2 / Number of copies: 2 / Classification: DNA
Source (natural)Organism: DNA molecule (others)
Molecular weightTheoretical: 6.456146 KDa
SequenceString:
(DG)(DC)(DT)(DG)(DC)(DG)(DA)(DG)(DA)(DT) (DC)(DC)(DG)(DC)(DT)(DC)(DC)(DG)(DG)(DT) (DG)

-
Macromolecule #3: EV272

MacromoleculeName: EV272 / type: dna / ID: 3 / Number of copies: 2 / Classification: DNA
Source (natural)Organism: DNA molecule (others)
Molecular weightTheoretical: 5.815762 KDa
SequenceString:
(DC)(DA)(DC)(DC)(DG)(DG)(DA)(DG)(DC)(DG) (DG)(DA)(DT)(DC)(DT)(DC)(DG)(DC)(DA)

-
Macromolecule #5: ZINC ION

MacromoleculeName: ZINC ION / type: ligand / ID: 5 / Number of copies: 16 / Formula: ZN
Molecular weightTheoretical: 65.409 Da

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 6.5
Sugar embeddingMaterial: vitreous ice
GridModel: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: GRAPHENE OXIDE / Support film - topology: HOLEY
Details: Graphene oxide was functionalised with amine-PEG4-DBCO
VitrificationCryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV
Details150 mM NaCl, 20 mM BisTris pH 6.5, 3mM CaCl2

-
Electron microscopy

MicroscopeTFS KRIOS
Specialist opticsEnergy filter - Name: TFS Selectris / Energy filter - Slit width: 7 eV
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 40.8 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.3000000000000003 µm / Nominal defocus min: 1.5 µm / Nominal magnification: 130000
Sample stageCooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: OTHER
Details: non-uniform refinement from cryosparc from smaller dataset collected on the same grid from Talos 200kV
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 4.5.3) / Number images used: 167347
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: RELION (ver. 4.0.0)
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 4.5.3)
Final 3D classificationSoftware - Name: cryoSPARC (ver. 4.5.3)
FSC plot (resolution estimation)

-
Atomic model buiding 1

Initial model
PDB IDChain

7u32

source_name: PDB, initial_model_type: experimental model

3hph

source_name: PDB, initial_model_type: experimental model
RefinementSpace: REAL / Protocol: RIGID BODY FIT
Output model

PDB-9s29:
MVV CSC intasome in complex with LEDGF

+
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