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Yorodumi- EMDB-8125: BG505 SOSIP.664 HIV-1 Env trimer in complex with anti-HIV fusion ... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-8125 | |||||||||
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Title | BG505 SOSIP.664 HIV-1 Env trimer in complex with anti-HIV fusion peptide targeting N123-VRC34.01 Fab | |||||||||
Map data | None | |||||||||
Sample |
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Function / homology | Function and homology information positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / viral protein processing / fusion of virus membrane with host plasma membrane / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / viral envelope ...positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / viral protein processing / fusion of virus membrane with host plasma membrane / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / apoptotic process / host cell plasma membrane / structural molecule activity / virion membrane / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Human immunodeficiency virus 1 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / negative staining / Resolution: 17.0 Å | |||||||||
Authors | Ozorowski G / Ward AB | |||||||||
Citation | Journal: Science / Year: 2016 Title: Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody. Authors: Rui Kong / Kai Xu / Tongqing Zhou / Priyamvada Acharya / Thomas Lemmin / Kevin Liu / Gabriel Ozorowski / Cinque Soto / Justin D Taft / Robert T Bailer / Evan M Cale / Lei Chen / Chang W Choi ...Authors: Rui Kong / Kai Xu / Tongqing Zhou / Priyamvada Acharya / Thomas Lemmin / Kevin Liu / Gabriel Ozorowski / Cinque Soto / Justin D Taft / Robert T Bailer / Evan M Cale / Lei Chen / Chang W Choi / Gwo-Yu Chuang / Nicole A Doria-Rose / Aliaksandr Druz / Ivelin S Georgiev / Jason Gorman / Jinghe Huang / M Gordon Joyce / Mark K Louder / Xiaochu Ma / Krisha McKee / Sijy O'Dell / Marie Pancera / Yongping Yang / Scott C Blanchard / Walther Mothes / Dennis R Burton / Wayne C Koff / Mark Connors / Andrew B Ward / Peter D Kwong / John R Mascola / Abstract: The HIV-1 fusion peptide, comprising 15 to 20 hydrophobic residues at the N terminus of the Env-gp41 subunit, is a critical component of the virus-cell entry machinery. Here, we report the ...The HIV-1 fusion peptide, comprising 15 to 20 hydrophobic residues at the N terminus of the Env-gp41 subunit, is a critical component of the virus-cell entry machinery. Here, we report the identification of a neutralizing antibody, N123-VRC34.01, which targets the fusion peptide and blocks viral entry by inhibiting conformational changes in gp120 and gp41 subunits of Env required for entry. Crystal structures of N123-VRC34.01 liganded to the fusion peptide, and to the full Env trimer, revealed an epitope consisting of the N-terminal eight residues of the gp41 fusion peptide and glycan N88 of gp120, and molecular dynamics showed that the N-terminal portion of the fusion peptide can be solvent-exposed. These results reveal the fusion peptide to be a neutralizing antibody epitope and thus a target for vaccine design. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_8125.map.gz | 14.5 MB | EMDB map data format | |
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Header (meta data) | emd-8125-v30.xml emd-8125.xml | 14.6 KB 14.6 KB | Display Display | EMDB header |
Images | emd_8125.png | 77.2 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-8125 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-8125 | HTTPS FTP |
-Validation report
Summary document | emd_8125_validation.pdf.gz | 78 KB | Display | EMDB validaton report |
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Full document | emd_8125_full_validation.pdf.gz | 77.1 KB | Display | |
Data in XML | emd_8125_validation.xml.gz | 494 B | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-8125 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-8125 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_8125.map.gz / Format: CCP4 / Size: 15.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | None | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.57 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : Complex containing 3 copies of N123-VRC34.01 anti-HIV Fab bound t...
Entire | Name: Complex containing 3 copies of N123-VRC34.01 anti-HIV Fab bound to a trimer of HIV-1 Env B505 SOSIP.664 |
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Components |
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-Supramolecule #1: Complex containing 3 copies of N123-VRC34.01 anti-HIV Fab bound t...
Supramolecule | Name: Complex containing 3 copies of N123-VRC34.01 anti-HIV Fab bound to a trimer of HIV-1 Env B505 SOSIP.664 type: complex / ID: 1 / Parent: 0 |
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Molecular weight | Theoretical: 570 KDa |
-Supramolecule #2: HIV-1 Env BG505 SOSIP.664
Supramolecule | Name: HIV-1 Env BG505 SOSIP.664 / type: complex / ID: 2 / Parent: 1 Details: Soluble and stabilized HIV-1 Env trimer from strain BG505. Engineered disulfide between A501C and T605C. I559P mutation to stabilize in pre-fusion state. Addition of N332 to restore ...Details: Soluble and stabilized HIV-1 Env trimer from strain BG505. Engineered disulfide between A501C and T605C. I559P mutation to stabilize in pre-fusion state. Addition of N332 to restore glycosylation site for purification and antigenic properties. Truncation after D664 to increase solubility. Formed with three gp140 subunits. |
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Source (natural) | Organism: Human immunodeficiency virus 1 / Strain: BG505 |
Recombinant expression | Organism: Homo sapiens (human) / Recombinant cell: HEK293F / Recombinant plasmid: pPPI4 |
-Supramolecule #3: Anti-HIV N123-VRC34.01 antibody fragment antigen binding
Supramolecule | Name: Anti-HIV N123-VRC34.01 antibody fragment antigen binding type: complex / ID: 3 / Parent: 1 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) / Recombinant cell: Expi 293 / Recombinant plasmid: pcDNA3.1 |
Molecular weight | Theoretical: 50 KDa |
-Experimental details
-Structure determination
Method | negative staining |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.03 mg/mL | |||||||||
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Buffer | pH: 7.4 Component:
Details: Sterile filtered buffer | |||||||||
Staining | Type: NEGATIVE / Material: 2% w/v uranyl formate Details: Negatively stained EM samples were prepared on carbon-coated Cu400 grids by applying sample for 10 seconds, blotting, applying 2% w/v uranyl formate for 45 seconds, and blotting again. | |||||||||
Grid | Model: EMS / Material: COPPER / Support film - Material: CARBON / Pretreatment - Type: PLASMA CLEANING | |||||||||
Details | Trimers were incubated with a 6-molar excess of Fab overnight at room temperature. |
-Electron microscopy
Microscope | FEI TECNAI 20 |
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Details | Collected a tilt series of -50, -40, -30, -20, -10, and 0 degrees. |
Image recording | Film or detector model: FEI CETA (4k x 4k) / Digitization - Dimensions - Width: 4096 pixel / Digitization - Dimensions - Height: 4096 pixel / Digitization - Sampling interval: 14.0 µm / Average electron dose: 25.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.5 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 92000 |
Sample stage | Specimen holder model: SIDE ENTRY, EUCENTRIC |