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- PDB-9bw9: Tetrameric Complex of full-length HIV-1 integrase protein bound t... -

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Basic information

Entry
Database: PDB / ID: 9bw9
TitleTetrameric Complex of full-length HIV-1 integrase protein bound to the integrase binding domain of LEDGF/p75
Components
  • Integrase
  • PC4 and SFRS1-interacting protein
KeywordsVIRAL PROTEIN / protein complex / hydrolase
Function / homology
Function and homology information


supercoiled DNA binding / Integration of viral DNA into host genomic DNA / Autointegration results in viral DNA circles / 2-LTR circle formation / Formation of WDR5-containing histone-modifying complexes / Vpr-mediated nuclear import of PICs / Integration of provirus / mRNA 5'-splice site recognition / APOBEC3G mediated resistance to HIV-1 infection / heterochromatin ...supercoiled DNA binding / Integration of viral DNA into host genomic DNA / Autointegration results in viral DNA circles / 2-LTR circle formation / Formation of WDR5-containing histone-modifying complexes / Vpr-mediated nuclear import of PICs / Integration of provirus / mRNA 5'-splice site recognition / APOBEC3G mediated resistance to HIV-1 infection / heterochromatin / nuclear periphery / HIV-1 retropepsin / symbiont-mediated activation of host apoptosis / retroviral ribonuclease H / exoribonuclease H / exoribonuclease H activity / euchromatin / host multivesicular body / DNA integration / viral genome integration into host DNA / RNA-directed DNA polymerase / establishment of integrated proviral latency / telomerase activity / viral penetration into host nucleus / RNA stem-loop binding / RNA-DNA hybrid ribonuclease activity / Transferases; Transferring phosphorus-containing groups; Nucleotidyltransferases / host cell / response to heat / viral nucleocapsid / DNA-binding transcription factor binding / DNA recombination / response to oxidative stress / DNA-directed DNA polymerase / aspartic-type endopeptidase activity / Hydrolases; Acting on ester bonds / DNA-directed DNA polymerase activity / transcription coactivator activity / chromatin remodeling / symbiont-mediated suppression of host gene expression / symbiont entry into host cell / viral translational frameshifting / lipid binding / chromatin binding / host cell nucleus / host cell plasma membrane / virion membrane / structural molecule activity / positive regulation of transcription by RNA polymerase II / proteolysis / DNA binding / RNA binding / zinc ion binding / nucleoplasm / nucleus / membrane / cytosol
Similarity search - Function
Lens epithelium-derived growth factor, integrase-binding domain / HIV integrase-binding domain superfamily / Lens epithelium-derived growth factor (LEDGF) / TFIIS/LEDGF domain superfamily / domain with conserved PWWP motif / PWWP domain / PWWP domain profile. / PWWP domain / Reverse transcriptase connection / Reverse transcriptase connection domain ...Lens epithelium-derived growth factor, integrase-binding domain / HIV integrase-binding domain superfamily / Lens epithelium-derived growth factor (LEDGF) / TFIIS/LEDGF domain superfamily / domain with conserved PWWP motif / PWWP domain / PWWP domain profile. / PWWP domain / Reverse transcriptase connection / Reverse transcriptase connection domain / Reverse transcriptase thumb / Reverse transcriptase thumb domain / Integrase Zinc binding domain / Zinc finger integrase-type profile. / Integrase-like, N-terminal / Integrase DNA binding domain / Integrase, C-terminal domain superfamily, retroviral / Integrase, N-terminal zinc-binding domain / Integrase, C-terminal, retroviral / Integrase DNA binding domain profile. / Immunodeficiency lentiviral matrix, N-terminal / gag gene protein p17 (matrix protein) / RNase H / Integrase core domain / Integrase, catalytic core / Integrase catalytic domain profile. / Retropepsin-like catalytic domain / Matrix protein, lentiviral and alpha-retroviral, N-terminal / Retroviral nucleocapsid Gag protein p24, C-terminal domain / Gag protein p24 C-terminal domain / RNase H type-1 domain profile. / Ribonuclease H domain / Retropepsins / Retroviral aspartyl protease / Aspartyl protease, retroviral-type family profile. / Peptidase A2A, retrovirus, catalytic / Reverse transcriptase domain / Reverse transcriptase (RNA-dependent DNA polymerase) / Reverse transcriptase (RT) catalytic domain profile. / Retrovirus capsid, C-terminal / Retroviral matrix protein / 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 speciesHomo sapiens (human)
HIV-1 06TG.HT008 (virus)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.1 Å
AuthorsJing, T. / Shan, Z. / Lyumkis, D. / Biswas, A.
Funding support United States, 5items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI136680 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI146017 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI170855 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI039394 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI170791 United States
CitationJournal: Biorxiv / Year: 2025
Title: Oligomeric HIV-1 Integrase Structures Reveal Functional Plasticity for Intasome Assembly and RNA Binding
Authors: Jing, T. / Shan, Z. / Dinh, T. / Biswas, A. / Jang, S. / Greenwood, J. / Li, M. / Zhang, Z. / Gray, G. / Shin, H.J. / Zhou, B. / Passos, D. / Strutzenberg, T.S. / Aiyer, S. / Andrade, L. / ...Authors: Jing, T. / Shan, Z. / Dinh, T. / Biswas, A. / Jang, S. / Greenwood, J. / Li, M. / Zhang, Z. / Gray, G. / Shin, H.J. / Zhou, B. / Passos, D. / Strutzenberg, T.S. / Aiyer, S. / Andrade, L. / Zhang, Y. / Li, Z. / Craigie, R. / Engelman, A.N. / Kvaratskhelia, M. / Lyumkis, D.
History
DepositionMay 21, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 25, 2025Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
G: PC4 and SFRS1-interacting protein
H: PC4 and SFRS1-interacting protein
C: Integrase
D: Integrase
E: PC4 and SFRS1-interacting protein
F: PC4 and SFRS1-interacting protein
A: Integrase
B: Integrase


Theoretical massNumber of molelcules
Total (without water)183,6188
Polymers183,6188
Non-polymers00
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

#1: Protein
PC4 and SFRS1-interacting protein / CLL-associated antigen KW-7 / Dense fine speckles 70 kDa protein / DFS 70 / Lens epithelium-derived ...CLL-associated antigen KW-7 / Dense fine speckles 70 kDa protein / DFS 70 / Lens epithelium-derived growth factor / Transcriptional coactivator p75/p52


Mass: 10460.211 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PSIP1, DFS70, LEDGF, PSIP2
Production host: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria)
References: UniProt: O75475
#2: Protein
Integrase / IN


Mass: 35444.297 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HIV-1 06TG.HT008 (virus) / Gene: gag-pol
Production host: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria)
References: UniProt: P12497, Transferases; Transferring phosphorus-containing groups; Nucleotidyltransferases, Hydrolases; Acting on ester bonds
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: Full-length tetrameric HIV-1 integrase bound to LEDGF IBD
Type: COMPLEX / Entity ID: all / Source: MULTIPLE SOURCES
Molecular weightValue: 0.16 MDa / Experimental value: YES
Source (natural)Organism: HIV type 1 (virus)
Source (recombinant)Organism: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria)
Buffer solutionpH: 7.6
Buffer component
IDConc.NameFormulaBuffer-ID
150 mMTris-HCl1
2750 mMsodium chlorideNaCl1
35 mMDTT1
410 %glycerolC3H5(OH)31
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3
VitrificationInstrument: HOMEMADE PLUNGER / Cryogen name: ETHANE
Details: Cryo-EM grids were prepared by freezing using a manual plunger in cold room at 4C

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Electron microscopy imaging

Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company
MicroscopyModel: FEI TALOS ARCTICA
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal magnification: 45000 X / Nominal defocus max: 2500 nm / Nominal defocus min: 500 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm / Alignment procedure: COMA FREE
Specimen holderCryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingElectron dose: 26.5 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of real images: 2649
Image scansWidth: 3710 / Height: 3838 / Movie frames/image: 60 / Used frames/image: 1-50

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Processing

EM software
IDNameVersionCategory
2Leginonimage acquisition
4cryoSPARC4.7CTF correction
7Cootmodel fitting
8UCSF Chimeramodel fitting
10PHENIXmodel refinement
11cryoSPARC4.7initial Euler assignment
12cryoSPARC4.7final Euler assignment
14cryoSPARC4.73D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
SymmetryPoint symmetry: C2 (2 fold cyclic)
3D reconstructionResolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 102050 / Algorithm: FOURIER SPACE / Symmetry type: POINT
Atomic model buildingProtocol: FLEXIBLE FIT / Space: REAL / Target criteria: Correlation coefficient
Atomic model building
IDPDB-ID 3D fitting-IDAccession codeSource nameType
11ITG11ITGPDBexperimental model
21IHV11IHVPDBexperimental model
31WJA11WJAPDBexperimental model
43HPH13HPHPDBexperimental model

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