+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-30331 | |||||||||
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Title | The interface of H014 Fab binds to SARS-CoV-2 S | |||||||||
Map data | ||||||||||
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 / symbiont-mediated suppression of host innate immune response / 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 | Homo sapiens (human) / Severe acute respiratory syndrome coronavirus 2 | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||
Authors | Zhe L / Cao L / Deng Y / Sun Y / Wang N / Xie L / Rao Z / wang Y / Qin C / Wang X | |||||||||
Citation | Journal: Science / Year: 2020 Title: Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody. Authors: Zhe Lv / Yong-Qiang Deng / Qing Ye / Lei Cao / Chun-Yun Sun / Changfa Fan / Weijin Huang / Shihui Sun / Yao Sun / Ling Zhu / Qi Chen / Nan Wang / Jianhui Nie / Zhen Cui / Dandan Zhu / Neil ...Authors: Zhe Lv / Yong-Qiang Deng / Qing Ye / Lei Cao / Chun-Yun Sun / Changfa Fan / Weijin Huang / Shihui Sun / Yao Sun / Ling Zhu / Qi Chen / Nan Wang / Jianhui Nie / Zhen Cui / Dandan Zhu / Neil Shaw / Xiao-Feng Li / Qianqian Li / Liangzhi Xie / Youchun Wang / Zihe Rao / Cheng-Feng Qin / Xiangxi Wang / Abstract: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are no approved ...The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are no approved vaccines or therapeutics for treating COVID-19. Here we report a humanized monoclonal antibody, H014, that efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nanomolar concentrations by engaging the spike (S) receptor binding domain (RBD). H014 administration reduced SARS-CoV-2 titers in infected lungs and prevented pulmonary pathology in a human angiotensin-converting enzyme 2 mouse model. Cryo-electron microscopy characterization of the SARS-CoV-2 S trimer in complex with the H014 Fab fragment unveiled a previously uncharacterized conformational epitope, which was only accessible when the RBD was in an open conformation. Biochemical, cellular, virological, and structural studies demonstrated that H014 prevents attachment of SARS-CoV-2 to its host cell receptors. Epitope analysis of available neutralizing antibodies against SARS-CoV and SARS-CoV-2 uncovered broad cross-protective epitopes. Our results highlight a key role for antibody-based therapeutic interventions in the treatment of COVID-19. | |||||||||
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_30331.map.gz | 1.4 MB | EMDB map data format | |
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Header (meta data) | emd-30331-v30.xml emd-30331.xml | 13.7 KB 13.7 KB | Display Display | EMDB header |
Images | emd_30331.png | 175.7 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-30331 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30331 | HTTPS FTP |
-Validation report
Summary document | emd_30331_validation.pdf.gz | 318.9 KB | Display | EMDB validaton report |
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Full document | emd_30331_full_validation.pdf.gz | 318.4 KB | Display | |
Data in XML | emd_30331_validation.xml.gz | 6.1 KB | Display | |
Data in CIF | emd_30331_validation.cif.gz | 6.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30331 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30331 | HTTPS FTP |
-Related structure data
Related structure data | 7cahMC 7cabC 7cacC 7caiC 7cakC M: atomic model generated by this map C: citing same article (ref.) |
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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_30331.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.04 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : The interface of H014 Fab binds to SARS-CoV-2 S
Entire | Name: The interface of H014 Fab binds to SARS-CoV-2 S |
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Components |
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-Supramolecule #1: The interface of H014 Fab binds to SARS-CoV-2 S
Supramolecule | Name: The interface of H014 Fab binds to SARS-CoV-2 S / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) / Recombinant cell: HEK293 |
-Supramolecule #2: H014 Fab
Supramolecule | Name: H014 Fab / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Recombinant expression | Organism: Homo sapiens (human) / Recombinant cell: HEK293 |
-Supramolecule #3: SARS-CoV-2 S
Supramolecule | Name: SARS-CoV-2 S / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3 |
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-Macromolecule #1: Light chain of H014 Fab
Macromolecule | Name: Light chain of H014 Fab / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 11.724151 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: IVLTQSPFQS VSPKEKVTIT CRASQSISSN LHWYQQKPDQ SPKLLIKYAS QSISGIPSRF SGSGSGTDFT LTINSLEAED FGIYFCQQT NFWPYIFGQG TKLEIL |
-Macromolecule #2: Heavy chain of H014 Fab
Macromolecule | Name: Heavy chain of H014 Fab / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.694471 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: VQLVQSGAEV KKPGATVKIS CKVSGYSFSN YYIHWVKQAP GKSLEWIGYI DPFNGGTSDN LKFKGAATLT ADTSTDTAYM ELSSLRSED TAVYYCARSE YDPYYVMDYW GQGTTVTVSS ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS W NSGALTSG ...String: VQLVQSGAEV KKPGATVKIS CKVSGYSFSN YYIHWVKQAP GKSLEWIGYI DPFNGGTSDN LKFKGAATLT ADTSTDTAYM ELSSLRSED TAVYYCARSE YDPYYVMDYW GQGTTVTVSS ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS W NSGALTSG VHTFPAVLQS SGLYSLSSVV TVPSSSLGTQ TYICNVNHKP SNTKVDKKVE PKSC |
-Macromolecule #3: Spike protein S1
Macromolecule | Name: Spike protein S1 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 21.772391 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: NLCPFGEVFN ATRFASVYAW NRKRISNCVA DYSVLYNSAS FSTFKCYGVS PTKLNDLCFT NVYADSFVIR GDEVRQIAPG QTGKIADYN YKLPDDFTGC VIAWNSNNLD SKVGGNYNYL YRLFRKSNLK PFERDISTEI YQAGSTPCNG VEGFNCYFPL Q SYGFQPTN ...String: NLCPFGEVFN ATRFASVYAW NRKRISNCVA DYSVLYNSAS FSTFKCYGVS PTKLNDLCFT NVYADSFVIR GDEVRQIAPG QTGKIADYN YKLPDDFTGC VIAWNSNNLD SKVGGNYNYL YRLFRKSNLK PFERDISTEI YQAGSTPCNG VEGFNCYFPL Q SYGFQPTN GVGYQPYRVV VLSFELLHAP ATVCGP |
-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 QUANTUM (4k x 4k) / Average electron dose: 60.0 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: PDB ENTRY PDB model - PDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 844961 |
Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |