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Yorodumi- EMDB-30950: SARS-CoV-2 spike in complex with the CA521 neutralizing antibody ... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-30950 | |||||||||
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Title | SARS-CoV-2 spike in complex with the CA521 neutralizing antibody Fab (focused refinement on Fab-RBD) | |||||||||
Map data | Focused refinement on CA521 Fab-RBD | |||||||||
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 / membrane fusion / Attachment and Entry / 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 | Severe acute respiratory syndrome coronavirus 2 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
Authors | Liu C / Song D / Dou C | |||||||||
Citation | Journal: Commun Biol / Year: 2021 Title: Structure and function analysis of a potent human neutralizing antibody CA521 against SARS-CoV-2. Authors: Deyong Song / Wenbo Wang / Chuangchuang Dong / Zhenfei Ning / Xiu Liu / Chuan Liu / Guangying Du / Chunjie Sha / Kailin Wang / Jun Lu / Baiping Sun / Yanyan Zhao / Qiaoping Wang / Hongguang ...Authors: Deyong Song / Wenbo Wang / Chuangchuang Dong / Zhenfei Ning / Xiu Liu / Chuan Liu / Guangying Du / Chunjie Sha / Kailin Wang / Jun Lu / Baiping Sun / Yanyan Zhao / Qiaoping Wang / Hongguang Xu / Ying Li / Zhenduo Shen / Jie Jiao / Ruiying Wang / Jingwei Tian / Wanhui Liu / Lan Wang / Yong-Qiang Deng / Changlin Dou / Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing COVID-19 pandemic, which has resulted in more than two million deaths at 2021 February . There is ...Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing COVID-19 pandemic, which has resulted in more than two million deaths at 2021 February . There is currently no approved therapeutics for treating COVID-19. The SARS-CoV-2 Spike protein is considered a key therapeutic target by many researchers. Here we describe the identification of several monoclonal antibodies that target SARS-CoV-2 Spike protein. One human antibody, CA521, demonstrated neutralization potential by immunizing human antibody transgenic mice. CA521 showed potent SARS-CoV-2-specific neutralization activity against SARS-CoV-2 pseudovirus and authentic SARS-CoV-2 infection in vitro. CA521 also demonstrated having a long half-life of 9.5 days in mice and 9.3 days in rhesus monkeys. CA521 inhibited SARS-CoV-2 infection in SARS-CoV-2 susceptible mice at a therapeutic setting with virus titer of the lung reduced by 4.5 logs. Structural analysis by cryo-EM revealed that CA521 recognizes an epitope overlapping with angiotensin converting enzyme 2 (ACE2)-binding sites in SARS-CoV-2 RBD in the Spike protein. CA521 blocks the interaction by binding all three RBDs of one SARS-CoV-2 spike trimer simultaneously. These results demonstrate the importance for antibody-based therapeutic interventions against COVID-19 and identifies CA521 a promising antibody that reacts with SARS-CoV-2 Spike protein to strongly neutralize its activity. | |||||||||
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_30950.map.gz | 63.2 MB | EMDB map data format | |
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Header (meta data) | emd-30950-v30.xml emd-30950.xml | 14.6 KB 14.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_30950_fsc.xml | 11.4 KB | Display | FSC data file |
Images | emd_30950.png | 37 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-30950 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30950 | HTTPS FTP |
-Validation report
Summary document | emd_30950_validation.pdf.gz | 473.6 KB | Display | EMDB validaton report |
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Full document | emd_30950_full_validation.pdf.gz | 473.2 KB | Display | |
Data in XML | emd_30950_validation.xml.gz | 12.3 KB | Display | |
Data in CIF | emd_30950_validation.cif.gz | 16.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30950 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30950 | HTTPS FTP |
-Related structure data
Related structure data | 7e23MC 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_30950.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Focused refinement on CA521 Fab-RBD | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.08 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 : CA521 Fab-RBD sub-complex
Entire | Name: CA521 Fab-RBD sub-complex |
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Components |
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-Supramolecule #1: CA521 Fab-RBD sub-complex
Supramolecule | Name: CA521 Fab-RBD sub-complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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-Supramolecule #2: Spike protein S1 2
Supramolecule | Name: Spike protein S1 2 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Recombinant expression | Organism: Homo sapiens (human) |
-Supramolecule #3: CA521 Heavy Chain
Supramolecule | Name: CA521 Heavy Chain / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
-Supramolecule #4: CA521 Light Chain
Supramolecule | Name: CA521 Light Chain / type: complex / ID: 4 / Parent: 1 / Macromolecule list: #3 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
-Macromolecule #1: Spike protein S1
Macromolecule | Name: Spike protein S1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 21.776381 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: TNLCPFGEVF NATRFASVYA WNRKRISNCV ADYSVLYNSA SFSTFKCYGV SPTKLNDLCF TNVYADSFVI RGDEVRQIAP GQTGKIADY NYKLPDDFTG CVIAWNSNNL DSKVGGNYNY LYRLFRKSNL KPFERDISTE IYQAGSTPCN GVEGFNCYFP L QSYGFQPT ...String: TNLCPFGEVF NATRFASVYA WNRKRISNCV ADYSVLYNSA SFSTFKCYGV SPTKLNDLCF TNVYADSFVI RGDEVRQIAP GQTGKIADY NYKLPDDFTG CVIAWNSNNL DSKVGGNYNY LYRLFRKSNL KPFERDISTE IYQAGSTPCN GVEGFNCYFP L QSYGFQPT NGVGYQPYRV VVLSFELLHA PATVCG |
-Macromolecule #2: CA521 Heavy Chain
Macromolecule | Name: CA521 Heavy Chain / 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: 49.120105 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: EVQLQQWGAG LLKPSETLSL TCAVYGGSFS GYYWSWIRQP PGKGLEWIGE VNHSGSTNYN PSLKSRVTIS VDTSKNQLSL KLNSVTAAD TAVYYCARGN TMVRGVIIPF EYWDKGTLVT VSSASTKGPS VFPLAPCSRS TSESTAALGC LVKDYFPEPV T VSWNSGAL ...String: EVQLQQWGAG LLKPSETLSL TCAVYGGSFS GYYWSWIRQP PGKGLEWIGE VNHSGSTNYN PSLKSRVTIS VDTSKNQLSL KLNSVTAAD TAVYYCARGN TMVRGVIIPF EYWDKGTLVT VSSASTKGPS VFPLAPCSRS TSESTAALGC LVKDYFPEPV T VSWNSGAL TSGVHTFPAV LQSSGLYSLS SVVTVPSSSL GTKTYTCNVD HKPSNTKVDK RVESKYGPPC PPCPAPEAAG GP SVFLFPP KPKDTLMISR TPEVTCVVVD VSQEDPEVQF NWYVDGVEVH NAKTKPREEQ FNSTYRVVSV LTVLHQDWLN GKE YKCKVS NKGLPSSIEK TISKAKGQPR EPQVYTLPPS QEEMTKNQVS LTCLVKGFYP SDIAVEWESN GQPENNYKTT PPVL DSDGS FFLYSRLTVD KSRWQEGNVF SCSVMHEALH NHYTQKSLSL SLG |
-Macromolecule #3: CA521 Light Chain
Macromolecule | Name: CA521 Light Chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.350908 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: EIVLTQSPAT LSLSPGERAT LSCRASQSVS SYLAWYQQKP GQAPRLLIYD ASNRATGIPA RFSGSGSGTD FTLTISSLEP EDFAVYYCQ QRSNWPLTFG GGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS ...String: EIVLTQSPAT LSLSPGERAT LSCRASQSVS SYLAWYQQKP GQAPRLLIYD ASNRATGIPA RFSGSGSGTD FTLTISSLEP EDFAVYYCQ QRSNWPLTFG GGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC |
-Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 1 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-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 K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 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 |