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Yorodumi- EMDB-20740: HIV-1 bNAb 1-55 in complex with modified BG505 SOSIP-based immuno... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-20740 | |||||||||
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Title | HIV-1 bNAb 1-55 in complex with modified BG505 SOSIP-based immunogen RC1 and 10-1074 | |||||||||
Map data | HIV-1 bNAb 1-55 in complex with modified BG505 SOSIP-based immunogen RC1 and 10-1074 | |||||||||
Sample |
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Keywords | HIV-1 broadly neutralizing antibody / bNAb / Env trimer / cryo-EM / RC1 / CD4-binding site / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
Function / homology | Function and homology information immunoglobulin complex / immunoglobulin mediated immune response / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / antigen binding / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / blood microparticle / adaptive immune response ...immunoglobulin complex / immunoglobulin mediated immune response / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / antigen binding / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / blood microparticle / adaptive immune response / viral protein processing / immune response / 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 / extracellular space / extracellular region / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Human immunodeficiency virus 1 | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||
Authors | Abernathy ME / Barnes CO / Gristick HB / Bjorkman PJ | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Cell / Year: 2020 Title: Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody. Authors: Philipp Schommers / Henning Gruell / Morgan E Abernathy / My-Kim Tran / Adam S Dingens / Harry B Gristick / Christopher O Barnes / Till Schoofs / Maike Schlotz / Kanika Vanshylla / Christoph ...Authors: Philipp Schommers / Henning Gruell / Morgan E Abernathy / My-Kim Tran / Adam S Dingens / Harry B Gristick / Christopher O Barnes / Till Schoofs / Maike Schlotz / Kanika Vanshylla / Christoph Kreer / Daniela Weiland / Udo Holtick / Christof Scheid / Markus M Valter / Marit J van Gils / Rogier W Sanders / Jörg J Vehreschild / Oliver A Cornely / Clara Lehmann / Gerd Fätkenheuer / Michael S Seaman / Jesse D Bloom / Pamela J Bjorkman / Florian Klein / Abstract: Broadly neutralizing antibodies (bNAbs) represent a promising approach to prevent and treat HIV-1 infection. However, viral escape through mutation of the HIV-1 envelope glycoprotein (Env) limits ...Broadly neutralizing antibodies (bNAbs) represent a promising approach to prevent and treat HIV-1 infection. However, viral escape through mutation of the HIV-1 envelope glycoprotein (Env) limits clinical applications. Here we describe 1-18, a new V1-46-encoded CD4 binding site (CD4bs) bNAb with outstanding breadth (97%) and potency (GeoMean IC = 0.048 μg/mL). Notably, 1-18 is not susceptible to typical CD4bs escape mutations and effectively overcomes HIV-1 resistance to other CD4bs bNAbs. Moreover, mutational antigenic profiling uncovered restricted pathways of HIV-1 escape. Of most promise for therapeutic use, even 1-18 alone fully suppressed viremia in HIV-1-infected humanized mice without selecting for resistant viral variants. A 2.5-Å cryo-EM structure of a 1-18-BG505 Env complex revealed that these characteristics are likely facilitated by a heavy-chain insertion and increased inter-protomer contacts. The ability of 1-18 to effectively restrict HIV-1 escape pathways provides a new option to successfully prevent and treat HIV-1 infection. | |||||||||
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_20740.map.gz | 32.1 MB | EMDB map data format | |
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Header (meta data) | emd-20740-v30.xml emd-20740.xml | 29.3 KB 29.3 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_20740_fsc.xml | 7.4 KB | Display | FSC data file |
Images | emd_20740.png | 119.6 KB | ||
Masks | emd_20740_msk_1.map | 34.3 MB | Mask map | |
Filedesc metadata | emd-20740.cif.gz | 8 KB | ||
Others | emd_20740_half_map_1.map.gz emd_20740_half_map_2.map.gz | 26.2 MB 26.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-20740 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-20740 | HTTPS FTP |
-Validation report
Summary document | emd_20740_validation.pdf.gz | 873 KB | Display | EMDB validaton report |
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Full document | emd_20740_full_validation.pdf.gz | 872.6 KB | Display | |
Data in XML | emd_20740_validation.xml.gz | 14.6 KB | Display | |
Data in CIF | emd_20740_validation.cif.gz | 18.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20740 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20740 | HTTPS FTP |
-Related structure data
Related structure data | 6udkMC 6udjC 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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Related items in Molecule of the Month |
-Map
File | Download / File: emd_20740.map.gz / Format: CCP4 / Size: 34.3 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | HIV-1 bNAb 1-55 in complex with modified BG505 SOSIP-based immunogen RC1 and 10-1074 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.4 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_20740_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_20740_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_20740_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Complex of three bNAb 1-55 Fabs and three 10-1074 Fabs bound to R...
+Supramolecule #1: Complex of three bNAb 1-55 Fabs and three 10-1074 Fabs bound to R...
+Supramolecule #2: 10-1074 Fab
+Supramolecule #3: 1-55 Fab
+Supramolecule #4: RC1 variant of HIV-1 BG505 SOSIP.664
+Macromolecule #1: RC1 variant of HIV-1 Env glycoprotein gp120
+Macromolecule #2: 10-1074 Fab Heavy Chain
+Macromolecule #3: 10-1074 Fab Light Chain
+Macromolecule #4: 1-55 Fab Heavy Chain
+Macromolecule #5: 1-55 Fab Light Chain
+Macromolecule #6: RC1 variant of HIV-1 Env glycoprotein gp41
+Macromolecule #13: 2-acetamido-2-deoxy-beta-D-glucopyranose
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.75 mg/mL | |||||||||
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Buffer | pH: 8 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec. / Pretreatment - Atmosphere: AIR | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 295 K / Instrument: FEI VITROBOT MARK IV Details: 0 blot force, 3.5 second blot time, 3 uL sample added to freshly glow-discharged grids. |
-Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Detector mode: COUNTING / Number grids imaged: 1 / Number real images: 684 / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 3.4 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 73000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Initial model |
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Refinement | Protocol: RIGID BODY FIT | ||||||||||||||
Output model | PDB-6udk: |