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Yorodumi- EMDB-24300: SARS-CoV-2 spike in complex with the S2D106 neutralizing antibody... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-24300 | |||||||||
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Title | SARS-CoV-2 spike in complex with the S2D106 neutralizing antibody Fab fragment | |||||||||
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Sample |
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Function / homology | Function and homology information Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell ...Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / membrane fusion / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / host cell surface receptor binding / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / identical protein binding / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | Severe acute respiratory syndrome coronavirus 2 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.67 Å | |||||||||
Authors | Park YJ / Veesler D | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Nature / Year: 2021 Title: SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape. Authors: Tyler N Starr / Nadine Czudnochowski / Zhuoming Liu / Fabrizia Zatta / Young-Jun Park / Amin Addetia / Dora Pinto / Martina Beltramello / Patrick Hernandez / Allison J Greaney / Roberta ...Authors: Tyler N Starr / Nadine Czudnochowski / Zhuoming Liu / Fabrizia Zatta / Young-Jun Park / Amin Addetia / Dora Pinto / Martina Beltramello / Patrick Hernandez / Allison J Greaney / Roberta Marzi / William G Glass / Ivy Zhang / Adam S Dingens / John E Bowen / M Alejandra Tortorici / Alexandra C Walls / Jason A Wojcechowskyj / Anna De Marco / Laura E Rosen / Jiayi Zhou / Martin Montiel-Ruiz / Hannah Kaiser / Josh R Dillen / Heather Tucker / Jessica Bassi / Chiara Silacci-Fregni / Michael P Housley / Julia di Iulio / Gloria Lombardo / Maria Agostini / Nicole Sprugasci / Katja Culap / Stefano Jaconi / Marcel Meury / Exequiel Dellota / Rana Abdelnabi / Shi-Yan Caroline Foo / Elisabetta Cameroni / Spencer Stumpf / Tristan I Croll / Jay C Nix / Colin Havenar-Daughton / Luca Piccoli / Fabio Benigni / Johan Neyts / Amalio Telenti / Florian A Lempp / Matteo S Pizzuto / John D Chodera / Christy M Hebner / Herbert W Virgin / Sean P J Whelan / David Veesler / Davide Corti / Jesse D Bloom / Gyorgy Snell / Abstract: An ideal therapeutic anti-SARS-CoV-2 antibody would resist viral escape, have activity against diverse sarbecoviruses, and be highly protective through viral neutralization and effector functions. ...An ideal therapeutic anti-SARS-CoV-2 antibody would resist viral escape, have activity against diverse sarbecoviruses, and be highly protective through viral neutralization and effector functions. Understanding how these properties relate to each other and vary across epitopes would aid the development of therapeutic antibodies and guide vaccine design. Here we comprehensively characterize escape, breadth and potency across a panel of SARS-CoV-2 antibodies targeting the receptor-binding domain (RBD). Despite a trade-off between in vitro neutralization potency and breadth of sarbecovirus binding, we identify neutralizing antibodies with exceptional sarbecovirus breadth and a corresponding resistance to SARS-CoV-2 escape. One of these antibodies, S2H97, binds with high affinity across all sarbecovirus clades to a cryptic epitope and prophylactically protects hamsters from viral challenge. Antibodies that target the angiotensin-converting enzyme 2 (ACE2) receptor-binding motif (RBM) typically have poor breadth and are readily escaped by mutations despite high neutralization potency. Nevertheless, we also characterize a potent RBM antibody (S2E12) with breadth across sarbecoviruses related to SARS-CoV-2 and a high barrier to viral escape. These data highlight principles underlying variation in escape, breadth and potency among antibodies that target the RBD, and identify epitopes and features to prioritize for therapeutic development against the current and potential future pandemics. | |||||||||
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_24300.map.gz | 230.2 MB | EMDB map data format | |
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Header (meta data) | emd-24300-v30.xml emd-24300.xml | 18.8 KB 18.8 KB | Display Display | EMDB header |
Images | emd_24300.png | 98.3 KB | ||
Others | emd_24300_additional_1.map.gz emd_24300_half_map_1.map.gz emd_24300_half_map_2.map.gz | 122.3 MB 226.3 MB 226.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-24300 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-24300 | HTTPS FTP |
-Validation report
Summary document | emd_24300_validation.pdf.gz | 552 KB | Display | EMDB validaton report |
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Full document | emd_24300_full_validation.pdf.gz | 551.6 KB | Display | |
Data in XML | emd_24300_validation.xml.gz | 16.1 KB | Display | |
Data in CIF | emd_24300_validation.cif.gz | 18.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24300 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24300 | 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_24300.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.05 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: #1
File | emd_24300_additional_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_24300_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_24300_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : SARS-CoV-2 spike in complex with the S2D106 neutralizing antibody...
Entire | Name: SARS-CoV-2 spike in complex with the S2D106 neutralizing antibody Fab fragment |
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Components |
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-Supramolecule #1: SARS-CoV-2 spike in complex with the S2D106 neutralizing antibody...
Supramolecule | Name: SARS-CoV-2 spike in complex with the S2D106 neutralizing antibody Fab fragment type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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-Supramolecule #2: SARS-CoV-2 spike
Supramolecule | Name: SARS-CoV-2 spike / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #2 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Recombinant expression | Organism: Homo sapiens (human) |
-Supramolecule #3: S2D106
Supramolecule | Name: S2D106 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #1, #3 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 70.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: OTHER / Details: cryoSPARC ab initio |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.67 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 175479 |
Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |