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Yorodumi- EMDB-36815: Recognition determinants of broad and potent HIV-1 neutralization... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-36815 | |||||||||||||||||||||
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Title | Recognition determinants of broad and potent HIV-1 neutralization by an affinity matured antibody from a pediatric elite-neutralizer | |||||||||||||||||||||
Map data | 44m Fab complex with HIV BG505.SOSIP envelope trimer | |||||||||||||||||||||
Sample |
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Keywords | A monoclonal antibody / HIV Trimer / Cryo-EM single particle / Structural analysis / ANTIVIRAL PROTEIN / VIRAL PROTEIN-ANTIVIRAL PROTEIN complex | |||||||||||||||||||||
Biological species | HIV-1 06TG.HT032 (virus) / Homo sapiens (human) | |||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.4 Å | |||||||||||||||||||||
Authors | Kumar S / Singh S / Chatterjee A / Bajpai P / Sharma S / Katpara S / Lodha R / Dutta S / Luthra K | |||||||||||||||||||||
Funding support | India, 6 items
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Citation | Journal: iScience / Year: 2023 Title: Recognition determinants of improved HIV-1 neutralization by a heavy chain matured pediatric antibody. Authors: Sanjeev Kumar / Swarandeep Singh / Arnab Chatterjee / Prashant Bajpai / Shaifali Sharma / Sanket Katpara / Rakesh Lodha / Somnath Dutta / Kalpana Luthra / Abstract: The structural and characteristic features of HIV-1 broadly neutralizing antibodies (bnAbs) from chronically infected pediatric donors are currently unknown. Herein, we characterized a heavy chain ...The structural and characteristic features of HIV-1 broadly neutralizing antibodies (bnAbs) from chronically infected pediatric donors are currently unknown. Herein, we characterized a heavy chain matured HIV-1 bnAb 44m, identified from a pediatric elite-neutralizer. Interestingly, in comparison to its wild-type AIIMS-P01 bnAb, 44m exhibited moderately higher level of somatic hypermutations of 15.2%. The 44m neutralized 79% of HIV-1 heterologous viruses (n = 58) tested, with a geometric mean IC titer of 0.36 μg/mL. The cryo-EM structure of 44m Fab in complex with fully cleaved glycosylated native-like BG505.SOSIP.664.T332N gp140 envelope trimer at 4.4 Å resolution revealed that 44m targets the V3-glycan N332-supersite and GDIR motif to neutralize HIV-1 with improved potency and breadth, plausibly attributed by a matured heavy chain as compared to that of wild-type AIIMS-P01. This study further improves our understanding on pediatric HIV-1 bnAbs and structural basis of broad HIV-1 neutralization by 44m may be useful blueprint for vaccine design in future. #1: Journal: To Be Published Title: Recognition determinants of broad and potent HIV-1 neutralization by an affinity matured antibody from a pediatric elite-neutralizer Authors: Kumar S / Singh S / Chatterjee A / Bajpai P / Sharma S / Katpara S / Lodha R / Dutta S / Luthra K | |||||||||||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_36815.map.gz | 78.2 MB | EMDB map data format | |
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Header (meta data) | emd-36815-v30.xml emd-36815.xml | 15.4 KB 15.4 KB | Display Display | EMDB header |
Images | emd_36815.png | 80.3 KB | ||
Filedesc metadata | emd-36815.cif.gz | 4.2 KB | ||
Others | emd_36815_half_map_1.map.gz emd_36815_half_map_2.map.gz | 65.3 MB 65.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-36815 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36815 | HTTPS FTP |
-Validation report
Summary document | emd_36815_validation.pdf.gz | 844.6 KB | Display | EMDB validaton report |
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Full document | emd_36815_full_validation.pdf.gz | 844.2 KB | Display | |
Data in XML | emd_36815_validation.xml.gz | 12.6 KB | Display | |
Data in CIF | emd_36815_validation.cif.gz | 14.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36815 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36815 | HTTPS FTP |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_36815.map.gz / Format: CCP4 / Size: 83.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | 44m Fab complex with HIV BG505.SOSIP envelope trimer | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.17 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: half map
File | emd_36815_half_map_1.map | ||||||||||||
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Annotation | half map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map
File | emd_36815_half_map_2.map | ||||||||||||
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Annotation | half map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : BG505 SOSIP trimer in complex with 44m bnAb
Entire | Name: BG505 SOSIP trimer in complex with 44m bnAb |
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Components |
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-Supramolecule #1: BG505 SOSIP trimer in complex with 44m bnAb
Supramolecule | Name: BG505 SOSIP trimer in complex with 44m bnAb / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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-Supramolecule #2: BG505 SOSIP trimer
Supramolecule | Name: BG505 SOSIP trimer / type: complex / ID: 2 / Parent: 1 / Details: HIV-1 trimer |
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Source (natural) | Organism: HIV-1 06TG.HT032 (virus) |
-Supramolecule #3: AIIMS 44m
Supramolecule | Name: AIIMS 44m / type: complex / ID: 3 / Parent: 2 / Details: monoclonal antibody |
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Source (natural) | Organism: Homo sapiens (human) |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 1.5 mg/mL |
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Buffer | pH: 8 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.25 µm / Nominal defocus min: 0.75 µm |
Sample stage | Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: OTHER |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 4.4 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 219374 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |