+Open data
-Basic information
Entry | Database: PDB / ID: 8eep | |||||||||
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Title | T=1 particle HIV-1 CA G60A/G61P | |||||||||
Components | Gag polyprotein | |||||||||
Keywords | VIRUS LIKE PARTICLE / HIV-1 / capsid / declination / pentamer / hexamer | |||||||||
Function / homology | Function and homology information viral process / viral nucleocapsid / host cell cytoplasm / host cell nucleus / structural molecule activity / virion membrane / RNA binding / zinc ion binding / ATP binding / cytoplasm Similarity search - Function | |||||||||
Biological species | Human immunodeficiency virus 1 | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.2 Å | |||||||||
Authors | Pornillos, O. / Ganser-Pornillos, B.K. / Schirra, R.T. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Nat Struct Mol Biol / Year: 2023 Title: A molecular switch modulates assembly and host factor binding of the HIV-1 capsid. Authors: Randall T Schirra / Nayara F B Dos Santos / Kaneil K Zadrozny / Iga Kucharska / Barbie K Ganser-Pornillos / Owen Pornillos / Abstract: The HIV-1 capsid is a fullerene cone made of quasi-equivalent hexamers and pentamers of the viral CA protein. Typically, quasi-equivalent assembly of viral capsid subunits is controlled by a ...The HIV-1 capsid is a fullerene cone made of quasi-equivalent hexamers and pentamers of the viral CA protein. Typically, quasi-equivalent assembly of viral capsid subunits is controlled by a molecular switch. Here, we identify a Thr-Val-Gly-Gly motif that modulates CA hexamer/pentamer switching by folding into a 3 helix in the pentamer and random coil in the hexamer. Manipulating the coil/helix configuration of the motif allowed us to control pentamer and hexamer formation in a predictable manner, thus proving its function as a molecular switch. Importantly, the switch also remodels the common binding site for host factors that are critical for viral replication and the new ultra-potent HIV-1 inhibitor lenacapavir. This study reveals that a critical assembly element also modulates the post-assembly and viral replication functions of the HIV-1 capsid and provides new insights on capsid function and inhibition. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8eep.cif.gz | 58.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8eep.ent.gz | 40.8 KB | Display | PDB format |
PDBx/mmJSON format | 8eep.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8eep_validation.pdf.gz | 1.5 MB | Display | wwPDB validaton report |
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Full document | 8eep_full_validation.pdf.gz | 1.5 MB | Display | |
Data in XML | 8eep_validation.xml.gz | 25 KB | Display | |
Data in CIF | 8eep_validation.cif.gz | 33.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ee/8eep ftp://data.pdbj.org/pub/pdb/validation_reports/ee/8eep | HTTPS FTP |
-Related structure data
Related structure data | 28054MC 7urnC 7urtC 8eetC 8ejlC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
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Symmetry | Point symmetry: (Schoenflies symbol: I (icosahedral)) |
-Components
#1: Protein | Mass: 25684.516 Da / Num. of mol.: 1 / Mutation: G60A, G61P Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Gene: gag / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: B6DRA0 | ||
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#2: Chemical | Has ligand of interest | Y | |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: T=1 particle of HIV-1 CA G60A/G61P/M66A / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Source (natural) | Organism: Human immunodeficiency virus 1 |
Source (recombinant) | Organism: Escherichia coli (E. coli) / Strain: BL21(DE3) |
Details of virus | Empty: YES / Enveloped: NO / Isolate: OTHER / Type: VIRUS-LIKE PARTICLE |
Buffer solution | pH: 6 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Instrument: HOMEMADE PLUNGER / Cryogen name: ETHANE / Details: Manual plunge-freezing |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 500 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.20.1_4487: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: I (icosahedral) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 494057 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: OTHER / Space: REAL Details: IP6 molecules were fit as rigid bodies in myo conformation | ||||||||||||||||||||||||
Atomic model building | PDB-ID: 4XFX Accession code: 4XFX / Source name: PDB / Type: experimental model | ||||||||||||||||||||||||
Refine LS restraints |
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