+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-24675 | ||||||||||||
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Title | AMC018 SOSIP.v4.2 in complex with PGV04 Fab | ||||||||||||
Map data | AMC018 SOSIP.v4.2 in complex with PGV04 Fab | ||||||||||||
Sample |
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Biological species | Human immunodeficiency virus 1 / Homo sapiens (human) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.49 Å | ||||||||||||
Authors | Cottrell CA / de Val N / Ward AB | ||||||||||||
Funding support | United States, 3 items
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Citation | Journal: J Virol / Year: 2022 Title: The Glycan Hole Area of HIV-1 Envelope Trimers Contributes Prominently to the Induction of Autologous Neutralization. Authors: Anna Schorcht / Christopher A Cottrell / Pavel Pugach / Rajesh P Ringe / Alvin X Han / Joel D Allen / Tom L G M van den Kerkhof / Gemma E Seabright / Edith E Schermer / Thomas J Ketas / ...Authors: Anna Schorcht / Christopher A Cottrell / Pavel Pugach / Rajesh P Ringe / Alvin X Han / Joel D Allen / Tom L G M van den Kerkhof / Gemma E Seabright / Edith E Schermer / Thomas J Ketas / Judith A Burger / Jelle van Schooten / Celia C LaBranche / Gabriel Ozorowski / Natalia de Val / Daniel L V Bader / Hanneke Schuitemaker / Colin A Russell / David C Montefiori / Marit J van Gils / Max Crispin / P J Klasse / Andrew B Ward / John P Moore / Rogier W Sanders / Abstract: The human immunodeficiency virus type 1 (HIV-1) trimeric envelope glycoprotein (Env) is heavily glycosylated, creating a dense glycan shield that protects the underlying peptidic surface from ...The human immunodeficiency virus type 1 (HIV-1) trimeric envelope glycoprotein (Env) is heavily glycosylated, creating a dense glycan shield that protects the underlying peptidic surface from antibody recognition. The absence of conserved glycans, due to missing potential N-linked glycosylation sites (PNGS), can result in strain-specific, autologous neutralizing antibody (NAb) responses. Here, we sought to gain a deeper understanding of the autologous neutralization by introducing holes in the otherwise dense glycan shields of the AMC011 and AMC016 SOSIP trimers. Specifically, when we knocked out the N130 and N289 glycans, which are absent from the well-characterized B41 SOSIP trimer, we observed stronger autologous NAb responses. We also analyzed the highly variable NAb responses induced in rabbits by diverse SOSIP trimers from subtypes A, B, and C. Statistical analysis, using linear regression, revealed that the cumulative area exposed on a trimer by glycan holes correlates with the magnitude of the autologous NAb response. Forty years after the first description of HIV-1, the search for a protective vaccine is still ongoing. The sole target for antibodies that can neutralize the virus are the trimeric envelope glycoproteins (Envs) located on the viral surface. The glycoprotein surface is covered with glycans that shield off the underlying protein components from recognition by the immune system. However, the Env trimers of some viral strains have holes in the glycan shield. Immunized animals developed antibodies against such glycan holes. These antibodies are generally strain specific. Here, we sought to gain a deeper understanding of what drives these specific immune responses. First, we show that strain-specific neutralizing antibody responses can be increased by creating artificial holes in the glycan shield. Second, when studying a diverse set of Env trimers with different characteristics, we found that the surface area of the glycan holes contributes prominently to the induction of strain-specific neutralizing antibodies. | ||||||||||||
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_24675.map.gz | 59.8 MB | EMDB map data format | |
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Header (meta data) | emd-24675-v30.xml emd-24675.xml | 20.4 KB 20.4 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_24675_fsc.xml | 8.9 KB | Display | FSC data file |
Images | emd_24675.png | 60.1 KB | ||
Others | emd_24675_half_map_1.map.gz emd_24675_half_map_2.map.gz | 59.3 MB 59.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-24675 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-24675 | HTTPS FTP |
-Validation report
Summary document | emd_24675_validation.pdf.gz | 838.8 KB | Display | EMDB validaton report |
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Full document | emd_24675_full_validation.pdf.gz | 838.3 KB | Display | |
Data in XML | emd_24675_validation.xml.gz | 16.2 KB | Display | |
Data in CIF | emd_24675_validation.cif.gz | 20.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24675 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24675 | HTTPS FTP |
-Related structure data
Related structure data | 7rsnMC 7rsoC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_24675.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | AMC018 SOSIP.v4.2 in complex with PGV04 Fab | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.31 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Half map: AMC018 SOSIP.v4.2 in complex with PGV04 Fab
File | emd_24675_half_map_1.map | ||||||||||||
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Annotation | AMC018 SOSIP.v4.2 in complex with PGV04 Fab | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: AMC018 SOSIP.v4.2 in complex with PGV04 Fab
File | emd_24675_half_map_2.map | ||||||||||||
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Annotation | AMC018 SOSIP.v4.2 in complex with PGV04 Fab | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : AMC018 SOSIP.v4.2 in complex with PGV04 Fab
Entire | Name: AMC018 SOSIP.v4.2 in complex with PGV04 Fab |
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Components |
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-Supramolecule #1: AMC018 SOSIP.v4.2 in complex with PGV04 Fab
Supramolecule | Name: AMC018 SOSIP.v4.2 in complex with PGV04 Fab / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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Source (natural) | Organism: Human immunodeficiency virus 1 |
-Macromolecule #1: AMC018 gp120
Macromolecule | Name: AMC018 gp120 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Human immunodeficiency virus 1 |
Molecular weight | Theoretical: 54.705789 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: AGNLWVTVYY GVPVWKEATT TLFCASDARA YETEARNVWA THACVPTDPN PQEVVLENVT ENFNMWRNNM VEQMHEDIIS LWDQSLKPC VKLTPLCVTL NCSDMGNETA TNNTSSGGET VEKGEIKNCS FNITTNIRDK VQKVYATFYK LDIVPIDDKT N NNNTNYTN ...String: AGNLWVTVYY GVPVWKEATT TLFCASDARA YETEARNVWA THACVPTDPN PQEVVLENVT ENFNMWRNNM VEQMHEDIIS LWDQSLKPC VKLTPLCVTL NCSDMGNETA TNNTSSGGET VEKGEIKNCS FNITTNIRDK VQKVYATFYK LDIVPIDDKT N NNNTNYTN YRLISCNTSV LTQACPKISF EPIPIHYCAP AGFAILKCNN KTFNGKGPCT NVSTVQCTHG IRPVVSTQLL LN GSLAEEE VVIRSENFTD NAKTIIVQLN ESVEINCTRP NNNTRRSISI GPGRWFYTTG EIIGNIRQAH CNISRAKWNN TLQ QIVNKL REKFENKTIV FNQPSGGDPE IVMHSFNCGG EFFYCNTTQL FNSTWNDTGG SNNTEGNNTI TLPCRIKQII NMWQ EVGKA MYAPPIKGQI RCSSNITGLL LTRDGGKTTN NTEIFRPGGG DMRDNWRSEL YKYKVVKIEP LGIAPTKCKR RVVQR RRRR R |
-Macromolecule #2: AMC018 gp41
Macromolecule | Name: AMC018 gp41 / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Human immunodeficiency virus 1 |
Molecular weight | Theoretical: 17.152566 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: AVGIGAVFLG FLGAAGSTMG AASMALTVQA RQLLSGIVQQ QNNLLRAPEA QQHMLKLTVW GIKQLQARVL AVERYLKDQQ LLGIWGCSG KLICCTAVPW NASWSNKSVD EIWGNMTWMQ WEREIDNYTS LIYTLIEESQ NQQEKNEQEL LELD |
-Macromolecule #3: PGV04 Fab heavy chain
Macromolecule | Name: PGV04 Fab heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 24.759861 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLVQSGSG VKKPGASVRV SCWTSEDIFE RTELIHWVRQ APGQGLEWIG WVKTVTGAVN FGSPDFRQRV SLTRDRDLFT AHMDIRGLT QGDTATYFCA RQKFYTGGQG WYFDLWGRGT LIVVSSASTK GPSVFPLAPS SKSTSGGTAA LGCLVKDYFP E PVTVSWNS ...String: QVQLVQSGSG VKKPGASVRV SCWTSEDIFE RTELIHWVRQ APGQGLEWIG WVKTVTGAVN FGSPDFRQRV SLTRDRDLFT AHMDIRGLT QGDTATYFCA RQKFYTGGQG WYFDLWGRGT LIVVSSASTK GPSVFPLAPS SKSTSGGTAA LGCLVKDYFP E PVTVSWNS GALTSGVHTF PAVLQSSGLY SLSSVVTVPS SSLGTQTYIC NVNHKPSNTK VDKKVEPKSC D |
-Macromolecule #4: PGV04 kappa chain
Macromolecule | Name: PGV04 kappa chain / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.073822 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EIVLTQSPGT LSLSPGETAS LSCTAASYGH MTWYQKKPGQ PPKLLIFATS KRASGIPDRF SGSQFGKQYT LTITRMEPED FARYYCQQL EFFGQGTRLE IRRTVAAPSV FIFPPSDEQL KSGTASVVCL LNNFYPREAK VQWKVDNALQ SGNSQESVTE Q DSKDSTYS ...String: EIVLTQSPGT LSLSPGETAS LSCTAASYGH MTWYQKKPGQ PPKLLIFATS KRASGIPDRF SGSQFGKQYT LTITRMEPED FARYYCQQL EFFGQGTRLE IRRTVAAPSV FIFPPSDEQL KSGTASVVCL LNNFYPREAK VQWKVDNALQ SGNSQESVTE Q DSKDSTYS LSSTLTLSKA DYEKHKVYAC EVTHQGLSSP VTKSFNRGEC |
-Macromolecule #9: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 9 / Number of copies: 30 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE / Instrument: HOMEMADE PLUNGER |
-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 / Number grids imaged: 1 / Number real images: 3916 / Average exposure time: 7.0 sec. / Average electron dose: 26.6 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: AB INITIO MODEL |
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Output model | PDB-7rsn: |