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Yorodumi- EMDB-20101: B41 SOSIP.664 trimer in complex with two Fab fragments of the sil... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-20101 | |||||||||
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Title | B41 SOSIP.664 trimer in complex with two Fab fragments of the silent-face targeting bNAb SF12, and one Fab fragment of the V3-targeting bNAb 10-1074 | |||||||||
Map data | Final sharpened map for class 2 | |||||||||
Sample |
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Biological species | Human immunodeficiency virus 1 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.36 Å | |||||||||
Authors | Barnes CO / Bjorkman PJ | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Immunity / Year: 2019 Title: Broad and Potent Neutralizing Antibodies Recognize the Silent Face of the HIV Envelope. Authors: Till Schoofs / Christopher O Barnes / Nina Suh-Toma / Jovana Golijanin / Philipp Schommers / Henning Gruell / Anthony P West / Franziska Bach / Yu Erica Lee / Lilian Nogueira / Ivelin S ...Authors: Till Schoofs / Christopher O Barnes / Nina Suh-Toma / Jovana Golijanin / Philipp Schommers / Henning Gruell / Anthony P West / Franziska Bach / Yu Erica Lee / Lilian Nogueira / Ivelin S Georgiev / Robert T Bailer / Julie Czartoski / John R Mascola / Michael S Seaman / M Juliana McElrath / Nicole A Doria-Rose / Florian Klein / Michel C Nussenzweig / Pamela J Bjorkman / Abstract: Broadly neutralizing antibodies (bNAbs) against HIV-1 envelope (Env) inform vaccine design and are potential therapeutic agents. We identified SF12 and related bNAbs with up to 62% neutralization ...Broadly neutralizing antibodies (bNAbs) against HIV-1 envelope (Env) inform vaccine design and are potential therapeutic agents. We identified SF12 and related bNAbs with up to 62% neutralization breadth from an HIV-infected donor. SF12 recognized a glycan-dominated epitope on Env's silent face and was potent against clade AE viruses, which are poorly covered by V3-glycan bNAbs. A 3.3Å cryo-EM structure of a SF12-Env trimer complex showed additional contacts to Env protein residues by SF12 compared with VRC-PG05, the only other known donor-derived silentface antibody, explaining SF12's increased neutralization breadth, potency, and resistance to Env mutation routes. Asymmetric binding of SF12 was associated with distinct N-glycan conformations across Env protomers, demonstrating intra-Env glycan heterogeneity. Administrating SF12 to HIV-1-infected humanized mice suppressed viremia and selected for viruses lacking the N448 glycan. Effective bNAbs can therefore be raised against HIV-1 Env's silent face, suggesting their potential for HIV-1 prevention, therapy, and vaccine development. | |||||||||
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_20101.map.gz | 10.7 MB | EMDB map data format | |
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Header (meta data) | emd-20101-v30.xml emd-20101.xml | 21.7 KB 21.7 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_20101_fsc.xml | 9.2 KB | Display | FSC data file |
Images | emd_20101.png | 144.8 KB | ||
Others | emd_20101_additional.map.gz emd_20101_half_map_1.map.gz emd_20101_half_map_2.map.gz | 48.9 MB 49.5 MB 49.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-20101 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-20101 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_20101.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Final sharpened map for class 2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.09 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: Unsharpened refined map
File | emd_20101_additional.map | ||||||||||||
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Annotation | Unsharpened refined map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map 1
File | emd_20101_half_map_1.map | ||||||||||||
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Annotation | half map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map 2
File | emd_20101_half_map_2.map | ||||||||||||
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Annotation | half map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Complex of B41 SOSIP.664 trimer with three SF12 Fabs and one 10-1...
Entire | Name: Complex of B41 SOSIP.664 trimer with three SF12 Fabs and one 10-1074 Fab. |
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Components |
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-Supramolecule #1: Complex of B41 SOSIP.664 trimer with three SF12 Fabs and one 10-1...
Supramolecule | Name: Complex of B41 SOSIP.664 trimer with three SF12 Fabs and one 10-1074 Fab. type: complex / ID: 1 / Parent: 0 Details: Fab fragment generated by recombinant expression and complexed with the B41 SOSIP.664 trimer |
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Molecular weight | Theoretical: 540 KDa |
-Supramolecule #2: B41 SOSIP.664 trimer
Supramolecule | Name: B41 SOSIP.664 trimer / type: complex / ID: 2 / Parent: 1 |
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Source (natural) | Organism: Human immunodeficiency virus 1 |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
-Supramolecule #3: 10-1074 Fab
Supramolecule | Name: 10-1074 Fab / type: complex / ID: 3 / Parent: 1 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) / Recombinant strain: Expi293 / Recombinant plasmid: p3BNC |
-Supramolecule #4: SF12 Fab
Supramolecule | Name: SF12 Fab / type: complex / ID: 4 / Parent: 1 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) / Recombinant strain: Expi293 / Recombinant plasmid: p3BNC |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.8 mg/mL | |||||||||
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Buffer | pH: 8 Component:
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Grid | Support film - Material: CARBON / Support film - topology: HOLEY / Details: unspecified | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 295 K / Instrument: FEI VITROBOT MARK IV Details: 0 blot force, 3 second blot time, 3 uL sample added to freshly glow-discharged grids. |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.2 µm / Nominal magnification: 130000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Digitization - Frames/image: 1-40 / Number grids imaged: 1 / Number real images: 2732 / Average exposure time: 8.0 sec. / Average electron dose: 40.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |