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Open data
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Basic information
Entry | Database: PDB / ID: 6vws | |||||||||
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Title | Hexamer of Helical HIV capsid by RASTR method | |||||||||
![]() | HIV capsid protein | |||||||||
![]() | VIRAL PROTEIN / Helical reconstruction / GS-6207 Hexamer HIV / RASTR | |||||||||
Function / homology | ![]() viral budding via host ESCRT complex / viral process / ISG15 antiviral mechanism / host multivesicular body / viral nucleocapsid / host cell cytoplasm / host cell nucleus / host cell plasma membrane / structural molecule activity / virion membrane ...viral budding via host ESCRT complex / viral process / ISG15 antiviral mechanism / host multivesicular body / viral nucleocapsid / host cell cytoplasm / host cell nucleus / host cell plasma membrane / structural molecule activity / virion membrane / RNA binding / zinc ion binding / ATP binding / membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 6.08 Å | |||||||||
![]() | Zhao, H. / Iqbal, N. / Asturias, F. / Kvaratskhelia, M. / Vanblerkom, P. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural and mechanistic bases for a potent HIV-1 capsid inhibitor. Authors: Stephanie M Bester / Guochao Wei / Haiyan Zhao / Daniel Adu-Ampratwum / Naseer Iqbal / Valentine V Courouble / Ashwanth C Francis / Arun S Annamalai / Parmit K Singh / Nikoloz Shkriabai / ...Authors: Stephanie M Bester / Guochao Wei / Haiyan Zhao / Daniel Adu-Ampratwum / Naseer Iqbal / Valentine V Courouble / Ashwanth C Francis / Arun S Annamalai / Parmit K Singh / Nikoloz Shkriabai / Peter Van Blerkom / James Morrison / Eric M Poeschla / Alan N Engelman / Gregory B Melikyan / Patrick R Griffin / James R Fuchs / Francisco J Asturias / Mamuka Kvaratskhelia / ![]() Abstract: The potent HIV-1 capsid inhibitor GS-6207 is an investigational principal component of long-acting antiretroviral therapy. We found that GS-6207 inhibits HIV-1 by stabilizing and thereby preventing ...The potent HIV-1 capsid inhibitor GS-6207 is an investigational principal component of long-acting antiretroviral therapy. We found that GS-6207 inhibits HIV-1 by stabilizing and thereby preventing functional disassembly of the capsid shell in infected cells. X-ray crystallography, cryo-electron microscopy, and hydrogen-deuterium exchange experiments revealed that GS-6207 tightly binds two adjoining capsid subunits and promotes distal intra- and inter-hexamer interactions that stabilize the curved capsid lattice. In addition, GS-6207 interferes with capsid binding to the cellular HIV-1 cofactors Nup153 and CPSF6 that mediate viral nuclear import and direct integration into gene-rich regions of chromatin. These findings elucidate structural insights into the multimodal, potent antiviral activity of GS-6207 and provide a means for rationally developing second-generation therapies. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 184.4 KB | Display | ![]() |
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PDB format | ![]() | 129.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 21423MC ![]() 6vkvC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 24613.174 Da / Num. of mol.: 6 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: HELICAL ARRAY / 3D reconstruction method: helical reconstruction |
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Sample preparation
Component | Name: Hexamer of helical HIV capsid protein / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 8 / Details: 1M NaCl, 50mM Tris pH 8.0 |
Specimen | Conc.: 3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: COPPER / Grid mesh size: 400 divisions/in. / Grid type: C-flat |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 298 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TALOS ARCTICA |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 28000 X / Calibrated magnification: 28000 X / Nominal defocus max: 2500 nm / Nominal defocus min: 1200 nm / Calibrated defocus min: 700 nm / Calibrated defocus max: 2000 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Temperature (max): 80 K / Temperature (min): 70 K |
Image recording | Electron dose: 47.36 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 4 / Num. of real images: 4246 |
Image scans | Width: 5760 / Height: 4092 |
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Processing
EM software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||||||||||||||||||||||||||||
Helical symmerty | Angular rotation/subunit: 150.32 ° / Axial rise/subunit: 7.61 Å / Axial symmetry: C1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 146291 Details: A total of 208,225helical segments were extracted from manually selected, well-ordered helical tubes using Relion | ||||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 6.08 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 245050 / Algorithm: BACK PROJECTION Details: A non-helical approach (RASTR) to calculate a volume from the same subset of data used for helical analysis. The position and rotation to the center of a single hexamer in the final helical ...Details: A non-helical approach (RASTR) to calculate a volume from the same subset of data used for helical analysis. The position and rotation to the center of a single hexamer in the final helical volume was determined and used along the final refined helical rise and twist to extract a total of 245050 unique particles from which surrounding tube density was subtracted by reprojection using Relion. The resulting stack of 245050 particles, each extracted into a 192 multiple 192 pixel box centered around the chosen asymmetric unit for each subtracted volume, was imported into Cryosparc. 2D clustering and ab-initio heterogeneous reconstruction with 4 volumes were then used to select a subset of 96392 particle images. These images, along with the cleanest reference from ab-initio volume determination were then used to obtain a volume through 3D Refinement. Num. of class averages: 96392 / Symmetry type: HELICAL | ||||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | B value: 204.64 / Protocol: RIGID BODY FIT / Space: REAL | ||||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 6VKV Pdb chain-ID: A / Accession code: 6VKV / Pdb chain residue range: 1-220 / Source name: PDB / Type: experimental model |