+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-0466 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | HIV-1 Env State 2A | |||||||||
Map data | Envelope | |||||||||
Sample |
| |||||||||
Biological species | Human immunodeficiency virus 1 | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 13.08 Å | |||||||||
Authors | Alsahafi N / Bakouche N / Kazemi M / Richard J / Ding S / Bhattacharyya S / Das D / Anand SP / Prevost J / Tolbert WD ...Alsahafi N / Bakouche N / Kazemi M / Richard J / Ding S / Bhattacharyya S / Das D / Anand SP / Prevost J / Tolbert WD / Lu H / Medjahed H / Delgado GGO / Kirk S / Melillo B / Mothes W / Sodroski J / Smith III AB / Kaufmann DE / Wu X / Pazgier M / Rouiller I / Finzi A / Munro JB | |||||||||
Citation | Journal: Cell Host Microbe / Year: 2019 Title: An Asymmetric Opening of HIV-1 Envelope Mediates Antibody-Dependent Cellular Cytotoxicity. Authors: Nirmin Alsahafi / Nordine Bakouche / Mohsen Kazemi / Jonathan Richard / Shilei Ding / Sudipta Bhattacharyya / Durba Das / Sai Priya Anand / Jérémie Prévost / William D Tolbert / Hong Lu / ...Authors: Nirmin Alsahafi / Nordine Bakouche / Mohsen Kazemi / Jonathan Richard / Shilei Ding / Sudipta Bhattacharyya / Durba Das / Sai Priya Anand / Jérémie Prévost / William D Tolbert / Hong Lu / Halima Medjahed / Gabrielle Gendron-Lepage / Gloria Gabrielle Ortega Delgado / Sharon Kirk / Bruno Melillo / Walther Mothes / Joseph Sodroski / Amos B Smith / Daniel E Kaufmann / Xueling Wu / Marzena Pazgier / Isabelle Rouiller / Andrés Finzi / James B Munro / Abstract: The HIV-1 envelope glycoprotein (Env) (gp120-gp41) is the target for neutralizing antibodies and antibody-dependent cellular cytotoxicity (ADCC). HIV-1 Env is flexible, sampling different ...The HIV-1 envelope glycoprotein (Env) (gp120-gp41) is the target for neutralizing antibodies and antibody-dependent cellular cytotoxicity (ADCC). HIV-1 Env is flexible, sampling different conformational states. Before engaging CD4, Env adopts a closed conformation (State 1) that is largely antibody resistant. CD4 binding induces an intermediate state (State 2), followed by an open conformation (State 3) that is susceptible to engagement by antibodies that recognize otherwise occluded epitopes. We investigate conformational changes in Env that induce ADCC in the presence of a small-molecule CD4-mimetic compound (CD4mc). We uncover an asymmetric Env conformation (State 2A) recognized by antibodies targeting the conserved gp120 inner domain and mediating ADCC. Sera from HIV+ individuals contain these antibodies, which can stabilize Env State 2A in combination with CD4mc. Additionally, triggering State 2A on HIV-infected primary CD4 T cells exposes epitopes that induce ADCC. Strategies that induce this Env conformation may represent approaches to fight HIV-1 infection. | |||||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_0466.map.gz | 27.8 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-0466-v30.xml emd-0466.xml | 14.2 KB 14.2 KB | Display Display | EMDB header |
Images | emd_0466.png | 41.5 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-0466 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-0466 | HTTPS FTP |
-Validation report
Summary document | emd_0466_validation.pdf.gz | 79.6 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_0466_full_validation.pdf.gz | 78.7 KB | Display | |
Data in XML | emd_0466_validation.xml.gz | 495 B | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0466 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0466 | HTTPS FTP |
-Related structure data
Similar structure data |
---|
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|
-Map
File | Download / File: emd_0466.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Envelope | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.7 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-Sample components
-Entire : HIV-1 Env in complex with BNM-III-170, A32 and 17b antibodies
Entire | Name: HIV-1 Env in complex with BNM-III-170, A32 and 17b antibodies |
---|---|
Components |
|
-Supramolecule #1: HIV-1 Env in complex with BNM-III-170, A32 and 17b antibodies
Supramolecule | Name: HIV-1 Env in complex with BNM-III-170, A32 and 17b antibodies type: complex / ID: 1 / Parent: 0 Details: HIV-1 Env present on the surface of Aldrithiol-2 (AT-2)-inactivated HIV-1 particles incubated with BNM-III-170, A32 and 17b antibodies. |
---|---|
Source (natural) | Organism: Human immunodeficiency virus 1 / Strain: HIV-1 BAL/SuPT1-CCR5 CL.30 |
Recombinant expression | Organism: Human immunodeficiency virus 1 / Recombinant strain: HIV-1 BAL/SuPT1-CCR5 CL.30 |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.335 mg/mL | ||||||||
---|---|---|---|---|---|---|---|---|---|
Buffer | pH: 7.2 Component:
| ||||||||
Grid | Model: Quantifoil R2/2 / Material: COPPER / Support film - Material: CARBON / Support film - topology: HOLEY / Support film - Film thickness: 2000.0 nm / Pretreatment - Type: GLOW DISCHARGE | ||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV | ||||||||
Details | Lot#P4311 |
-Electron microscopy
Microscope | FEI TALOS ARCTICA |
---|---|
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Digitization - Dimensions - Width: 3838 pixel / Digitization - Dimensions - Height: 3710 pixel / Number real images: 1033 / Average electron dose: 1.4 e/Å2 Details: 1033 was the number of initial images (movies) that 1032 were selected for particle picking |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Calibrated defocus max: 3.2076 µm / Calibrated defocus min: 1.1559 µm / Calibrated magnification: 79000 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm |
Sample stage | Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |