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- EMDB-20484: Structure of HIV cleaved synaptic complex (CSC) intasome bound wi... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-20484 | ||||||||||||
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Title | Structure of HIV cleaved synaptic complex (CSC) intasome bound with magnesium and INSTI XZ426 (compound 4d) | ||||||||||||
![]() | Structure of HIV cleaved synaptic complex intasome bound to 4d; sharpened | ||||||||||||
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![]() | integrase / intasome / transposition / VIRAL PROTEIN / VIRAL PROTEIN-DNA complex | ||||||||||||
Function / homology | ![]() RNA endonuclease activity / DNA integration / RNA stem-loop binding / RNA-directed DNA polymerase activity / endonuclease activity / DNA recombination / symbiont entry into host cell / DNA binding / zinc ion binding / cytoplasm Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.8 Å | ||||||||||||
![]() | Lyumkis D / Passos D | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis for strand-transfer inhibitor binding to HIV intasomes. Authors: Dario Oliveira Passos / Min Li / Ilona K Jóźwik / Xue Zhi Zhao / Diogo Santos-Martins / Renbin Yang / Steven J Smith / Youngmin Jeon / Stefano Forli / Stephen H Hughes / Terrence R Burke / ...Authors: Dario Oliveira Passos / Min Li / Ilona K Jóźwik / Xue Zhi Zhao / Diogo Santos-Martins / Renbin Yang / Steven J Smith / Youngmin Jeon / Stefano Forli / Stephen H Hughes / Terrence R Burke / Robert Craigie / Dmitry Lyumkis / ![]() Abstract: The HIV intasome is a large nucleoprotein assembly that mediates the integration of a DNA copy of the viral genome into host chromatin. Intasomes are targeted by the latest generation of ...The HIV intasome is a large nucleoprotein assembly that mediates the integration of a DNA copy of the viral genome into host chromatin. Intasomes are targeted by the latest generation of antiretroviral drugs, integrase strand-transfer inhibitors (INSTIs). Challenges associated with lentiviral intasome biochemistry have hindered high-resolution structural studies of how INSTIs bind to their native drug target. Here, we present high-resolution cryo-electron microscopy structures of HIV intasomes bound to the latest generation of INSTIs. These structures highlight how small changes in the integrase active site can have notable implications for drug binding and design and provide mechanistic insights into why a leading INSTI retains efficacy against a broad spectrum of drug-resistant variants. The data have implications for expanding effective treatments available for HIV-infected individuals. | ||||||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 200.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 27.6 KB 27.6 KB | Display Display | ![]() |
Images | ![]() | 88.1 KB | ||
Filedesc metadata | ![]() | 7.1 KB | ||
Others | ![]() ![]() ![]() ![]() | 196.6 MB 11.8 MB 26.4 MB 26.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6puyMC ![]() 6putC ![]() 6puwC ![]() 6puzC ![]() 6v3kC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | |
EM raw data | ![]() Data size: 4.4 TB Data #1: Aligned, summed and exposure weighted micrographs of HIV-1 intasome bound to compound 4d. [micrographs - single frame] Data #2: Unaligned raw movies of HIV-1 intasome bound to compound 4d [micrographs - multiframe]) |
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Links
EMDB pages | ![]() ![]() |
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Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Structure of HIV cleaved synaptic complex intasome bound to 4d; sharpened | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.79 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: Structure of HIV cleaved synaptic complex intasome bound...
File | emd_20484_additional_1.map | ||||||||||||
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Annotation | Structure of HIV cleaved synaptic complex intasome bound to 4d. Full map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: local resolution
File | emd_20484_additional_2.map | ||||||||||||
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Annotation | local resolution | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map 2
File | emd_20484_half_map_1.map | ||||||||||||
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Annotation | half map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map 1
File | emd_20484_half_map_2.map | ||||||||||||
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Annotation | half map 1 | ||||||||||||
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Density Histograms |
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Sample components
-Entire : Assembly of HIV integrase and viral DNA
Entire | Name: Assembly of HIV integrase and viral DNA |
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Components |
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-Supramolecule #1: Assembly of HIV integrase and viral DNA
Supramolecule | Name: Assembly of HIV integrase and viral DNA / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 400 KDa |
-Macromolecule #1: Chimeric Sso7d and HIV-1 integrase
Macromolecule | Name: Chimeric Sso7d and HIV-1 integrase / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 42.321258 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MGSSHHHHHH SSGLVPRGSH MATVKFKYKG EEKEVDISKI KKVWRVGKMI SFTYDEGGGK TGRGAVSEKD APKELLQMLE KQKKGGGGG GGGGGGFLDG IDKAQEEHEK YHSNWRAMAS DFNLPPVVAK EIVASCDKCQ LKGEAMHGQV DCSPGIWQLD C THLEGKVI ...String: MGSSHHHHHH SSGLVPRGSH MATVKFKYKG EEKEVDISKI KKVWRVGKMI SFTYDEGGGK TGRGAVSEKD APKELLQMLE KQKKGGGGG GGGGGGFLDG IDKAQEEHEK YHSNWRAMAS DFNLPPVVAK EIVASCDKCQ LKGEAMHGQV DCSPGIWQLD C THLEGKVI LVAVHVASGY IEAEVIPAET GQETAYFLLK LAGRWPVKTV HTDNGSNFTS TTVKAACWWA GIKQEFGIPY NP QSQGVIE SMNKELKKII GQVRDQAEHL KTAVQMAVFI HNFKRKGGIG GYSAGERIVD IIATDIQTKE LQKQITKIQN FRV YYRDSR DPVWKGPAKL LWKGEGAVVI QDNSDIKVVP RRKAKIIRDY GKQMAGDDCV ASRQDED UniProtKB: DNA-binding protein 7d, Integrase |
-Macromolecule #2: viral DNA non-transferred strand
Macromolecule | Name: viral DNA non-transferred strand / type: dna / ID: 2 / Number of copies: 1 / Classification: DNA |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 8.188271 KDa |
Sequence | String: (DA)(DC)(DT)(DG)(DC)(DT)(DA)(DG)(DA)(DG) (DA)(DT)(DT)(DT)(DT)(DC)(DC)(DC)(DG)(DC) (DC)(DC)(DA)(DC)(DG)(DC)(DT) |
-Macromolecule #3: viral DNA transferred strand
Macromolecule | Name: viral DNA transferred strand / type: dna / ID: 3 / Number of copies: 1 / Classification: DNA |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 7.773023 KDa |
Sequence | String: (DA)(DG)(DC)(DG)(DT)(DG)(DG)(DG)(DC)(DG) (DG)(DG)(DA)(DA)(DA)(DA)(DT)(DC)(DT)(DC) (DT)(DA)(DG)(DC)(DA) |
-Macromolecule #4: MAGNESIUM ION
Macromolecule | Name: MAGNESIUM ION / type: ligand / ID: 4 / Number of copies: 2 / Formula: MG |
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Molecular weight | Theoretical: 24.305 Da |
-Macromolecule #5: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 5 / Number of copies: 2 / Formula: ZN |
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Molecular weight | Theoretical: 65.409 Da |
-Macromolecule #6: 4-amino-N-[(2,4-difluorophenyl)methyl]-1-hydroxy-6-(6-hydroxyhexy...
Macromolecule | Name: 4-amino-N-[(2,4-difluorophenyl)methyl]-1-hydroxy-6-(6-hydroxyhexyl)-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxamide type: ligand / ID: 6 / Number of copies: 1 / Formula: OZ1 |
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Molecular weight | Theoretical: 446.447 Da |
Chemical component information | ![]() ChemComp-OZ1: |
-Macromolecule #7: water
Macromolecule | Name: water / type: ligand / ID: 7 / Number of copies: 202 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ![]() ChemComp-HOH: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.2 mg/mL | ||||||||||||||||||
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Buffer | pH: 6.2 Component:
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Grid | Model: UltrAuFoil / Material: GOLD / Mesh: 400 / Pretreatment - Type: PLASMA CLEANING / Pretreatment - Time: 7 sec. | ||||||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 80 % / Instrument: HOMEMADE PLUNGER |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Digitization - Dimensions - Width: 3838 pixel / Digitization - Dimensions - Height: 3710 pixel / Digitization - Frames/image: 4-80 / Number real images: 2024 / Average electron dose: 45.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 70.0 µm / Calibrated magnification: 63291 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.5 µm / Nominal magnification: 37000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Initial model |
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Refinement | Space: REAL / Protocol: FLEXIBLE FIT / Target criteria: Correlation coefficient | ||||||||
Output model | ![]() PDB-6puy: |