+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-23709 | ||||||||||||
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Title | SARS-CoV-2 Spike:Fab 3D11 complex focused refinement | ||||||||||||
Map data | SARS-CoV-2 Spike:Fab 3D11 complex, raw map from focused refinement of Fab and 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 / 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 | Severe acute respiratory syndrome coronavirus 2 / Homo sapiens (human) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.95 Å | ||||||||||||
Authors | Asarnow D / Cheng Y | ||||||||||||
Funding support | United States, 3 items
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Citation | Journal: Cell / Year: 2021 Title: Structural insight into SARS-CoV-2 neutralizing antibodies and modulation of syncytia. Authors: Daniel Asarnow / Bei Wang / Wen-Hsin Lee / Yuanyu Hu / Ching-Wen Huang / Bryan Faust / Patricia Miang Lon Ng / Eve Zi Xian Ngoh / Markus Bohn / David Bulkley / Andrés Pizzorno / Beatrice ...Authors: Daniel Asarnow / Bei Wang / Wen-Hsin Lee / Yuanyu Hu / Ching-Wen Huang / Bryan Faust / Patricia Miang Lon Ng / Eve Zi Xian Ngoh / Markus Bohn / David Bulkley / Andrés Pizzorno / Beatrice Ary / Hwee Ching Tan / Chia Yin Lee / Rabiatul Adawiyah Minhat / Olivier Terrier / Mun Kuen Soh / Frannie Jiuyi Teo / Yvonne Yee Chin Yeap / Shirley Gek Kheng Seah / Conrad En Zuo Chan / Emily Connelly / Nicholas J Young / Sebastian Maurer-Stroh / Laurent Renia / Brendon John Hanson / Manuel Rosa-Calatrava / Aashish Manglik / Yifan Cheng / Charles S Craik / Cheng-I Wang / Abstract: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is initiated by binding of the viral Spike protein to host receptor angiotensin-converting enzyme 2 (ACE2), followed by ...Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is initiated by binding of the viral Spike protein to host receptor angiotensin-converting enzyme 2 (ACE2), followed by fusion of viral and host membranes. Although antibodies that block this interaction are in emergency use as early coronavirus disease 2019 (COVID-19) therapies, the precise determinants of neutralization potency remain unknown. We discovered a series of antibodies that potently block ACE2 binding but exhibit divergent neutralization efficacy against the live virus. Strikingly, these neutralizing antibodies can inhibit or enhance Spike-mediated membrane fusion and formation of syncytia, which are associated with chronic tissue damage in individuals with COVID-19. As revealed by cryoelectron microscopy, multiple structures of Spike-antibody complexes have distinct binding modes that not only block ACE2 binding but also alter the Spike protein conformational cycle triggered by ACE2 binding. We show that stabilization of different Spike conformations leads to modulation of Spike-mediated membrane fusion with profound implications for COVID-19 pathology and immunity. | ||||||||||||
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_23709.map.gz | 89.4 MB | EMDB map data format | |
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Header (meta data) | emd-23709-v30.xml emd-23709.xml | 29.2 KB 29.2 KB | Display Display | EMDB header |
Images | emd_23709.png | 139.8 KB | ||
Masks | emd_23709_msk_1.map | 178 MB | Mask map | |
Others | emd_23709_additional_1.map.gz emd_23709_half_map_1.map.gz emd_23709_half_map_2.map.gz | 168.1 MB 165.3 MB 165.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-23709 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-23709 | HTTPS FTP |
-Validation report
Summary document | emd_23709_validation.pdf.gz | 800.6 KB | Display | EMDB validaton report |
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Full document | emd_23709_full_validation.pdf.gz | 800.2 KB | Display | |
Data in XML | emd_23709_validation.xml.gz | 14.8 KB | Display | |
Data in CIF | emd_23709_validation.cif.gz | 17.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23709 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23709 | HTTPS FTP |
-Related structure data
Related structure data | 7m7bMC 7kqbC 7kqeC 7m71C 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_23709.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | SARS-CoV-2 Spike:Fab 3D11 complex, raw map from focused refinement of Fab and RBD | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.18756 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_23709_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: SARS-CoV-2 Spike:Fab 3D11 complex, sharpened map from focused...
File | emd_23709_additional_1.map | ||||||||||||
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Annotation | SARS-CoV-2 Spike:Fab 3D11 complex, sharpened map from focused refinement of Fab and RBD | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: SARS-CoV-2 Spike:Fab 3D11 complex, half map 1 from...
File | emd_23709_half_map_1.map | ||||||||||||
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Annotation | SARS-CoV-2 Spike:Fab 3D11 complex, half map 1 from focused refinement of Fab and RBD | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: SARS-CoV-2 Spike:Fab 3D11 complex, half map 2 from...
File | emd_23709_half_map_2.map | ||||||||||||
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Annotation | SARS-CoV-2 Spike:Fab 3D11 complex, half map 2 from focused refinement of Fab and RBD | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : SARS-CoV-2 Spike protein trimer in complex with Fab 3D11
Entire | Name: SARS-CoV-2 Spike protein trimer in complex with Fab 3D11 |
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Components |
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-Supramolecule #1: SARS-CoV-2 Spike protein trimer in complex with Fab 3D11
Supramolecule | Name: SARS-CoV-2 Spike protein trimer in complex with Fab 3D11 type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Molecular weight | Theoretical: 457.1 KDa |
-Supramolecule #2: SARS-CoV-2 Spike protein trimer
Supramolecule | Name: SARS-CoV-2 Spike protein trimer / 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: Cricetulus griseus (Chinese hamster) / Recombinant strain: expiCHO / Recombinant cell: Ovary |
-Supramolecule #3: Fab 3D11
Supramolecule | Name: Fab 3D11 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
-Macromolecule #1: Spike glycoprotein
Macromolecule | Name: Spike glycoprotein / 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: 133.75325 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHAIHV SGTNGTKRFD NPVLPFNDG VYFASTEKSN IIRGWIFGTT LDSKTQSLLI VNNATNVVIK VCEFQFCNDP FLGVYYHKNN KSWMESEFRV Y SSANNCTF ...String: MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHAIHV SGTNGTKRFD NPVLPFNDG VYFASTEKSN IIRGWIFGTT LDSKTQSLLI VNNATNVVIK VCEFQFCNDP FLGVYYHKNN KSWMESEFRV Y SSANNCTF EYVSQPFLMD LEGKQGNFKN LREFVFKNID GYFKIYSKHT PINLVRDLPQ GFSALEPLVD LPIGINITRF QT LLALHRS YLTPGDSSSG WTAGAAAYYV GYLQPRTFLL KYNENGTITD AVDCALDPLS ETKCTLKSFT VEKGIYQTSN FRV QPTESI VRFPNITNLC PFGEVFNATR FASVYAWNRK RISNCVADYS VLYNSASFST FKCYGVSPTK LNDLCFTNVY ADSF VIRGD EVRQIAPGQT GKIADYNYKL PDDFTGCVIA WNSNNLDSKV GGNYNYLYRL FRKSNLKPFE RDISTEIYQA GSTPC NGVE GFNCYFPLQS YGFQPTNGVG YQPYRVVVLS FELLHAPATV CGPKKSTNLV KNKCVNFNFN GLTGTGVLTE SNKKFL PFQ QFGRDIADTT DAVRDPQTLE ILDITPCSFG GVSVITPGTN TSNQVAVLYQ DVNCTEVPVA IHADQLTPTW RVYSTGS NV FQTRAGCLIG AEHVNNSYEC DIPIGAGICA SYQTQTNSPG SASSVASQSI IAYTMSLGAE NSVAYSNNSI AIPTNFTI S VTTEILPVSM TKTSVDCTMY ICGDSTECSN LLLQYGSFCT QLNRALTGIA VEQDKNTQEV FAQVKQIYKT PPIKDFGGF NFSQILPDPS KPSKRSFIED LLFNKVTLAD AGFIKQYGDC LGDIAARDLI CAQKFNGLTV LPPLLTDEMI AQYTSALLAG TITSGWTFG AGAALQIPFA MQMAYRFNGI GVTQNVLYEN QKLIANQFNS AIGKIQDSLS STASALGKLQ DVVNQNAQAL N TLVKQLSS NFGAISSVLN DILSRLDPPE AEVQIDRLIT GRLQSLQTYV TQQLIRAAEI RASANLAATK MSECVLGQSK RV DFCGKGY HLMSFPQSAP HGVVFLHVTY VPAQEKNFTT APAICHDGKA HFPREGVFVS NGTHWFVTQR NFYEPQIITT DNT FVSGNC DVVIGIVNNT VYDPLQPELD SFKEELDKYF KNHTSPDVDL GDISGINASV VNIQKEIDRL NEVAKNLNES LIDL QELGK YEQ |
-Macromolecule #2: Antibody Fab 3D11 heavy chain
Macromolecule | Name: Antibody Fab 3D11 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: 49.110184 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: QVQLQQWGAG LLKPSETLSL TCAVYGGSFS GYYWSWIRQP PGKGLEWIGE INHSGSTNYN PSLKSRVTIS VDTSKNQFSL KLSSVTAAD TAVYYCARRW WLRGAFDIWG QGTTVTVSSA STKGPSVFPL APSSKSTSGG TAALGCLVKD YFPEPVTVSW N SGALTSGV ...String: QVQLQQWGAG LLKPSETLSL TCAVYGGSFS GYYWSWIRQP PGKGLEWIGE INHSGSTNYN PSLKSRVTIS VDTSKNQFSL KLSSVTAAD TAVYYCARRW WLRGAFDIWG QGTTVTVSSA STKGPSVFPL APSSKSTSGG TAALGCLVKD YFPEPVTVSW N SGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKRVEP KSCDKTHTCP PCPAPEAAGG PS VFLFPPK PKDTLMISRT PEVTCVVVDV SHEDPEVKFN WYVDGVEVHN AKTKPREEQY NSTYRVVSVL TVLHQDWLNG KEY KCKVSN KALPAPIEKT ISKAKGQPRE PQVYTLPPSR DELTKNQVSL TCLVKGFYPS DIAVEWESNG QPENNYKTTP PVLD SDGSF LLYSKLTVDK SRWQQGNVFS CSVMHEALHN HYTQKSLSLS PGK |
-Macromolecule #3: Antibody Fab 3D11 light chain
Macromolecule | Name: Antibody Fab 3D11 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: 23.055285 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: NFMLTQPHSV SASPGKTVTI PCTGSSGNIA SNYVQWYQQR PGSAPTTVIY EDNQRPSGVP DRFSGSIDSS SNSASLTISG LKTEDEADY YCQSYDNNIQ VFGGGTKLTV LGQPKAAPSV TLFPPSSEEL QANKATLVCL ISDFYPGAVT VAWKADSSPV K AGVETTTP ...String: NFMLTQPHSV SASPGKTVTI PCTGSSGNIA SNYVQWYQQR PGSAPTTVIY EDNQRPSGVP DRFSGSIDSS SNSASLTISG LKTEDEADY YCQSYDNNIQ VFGGGTKLTV LGQPKAAPSV TLFPPSSEEL QANKATLVCL ISDFYPGAVT VAWKADSSPV K AGVETTTP SKQSNNKYAA SSYLSLTPEQ WKSHRSYSCQ VTHEGSTVEK TVAPTECS |
-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: 2 / 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
Concentration | 0.4 mg/mL | |||||||||
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Buffer | pH: 8 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Atmosphere: AIR | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 4 K / Instrument: FEI VITROBOT MARK IV / Details: 8-10 seconds, blot force 0. |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Digitization - Dimensions - Width: 5760 pixel / Digitization - Dimensions - Height: 4092 pixel / Digitization - Sampling interval: 5.0 µm / Number grids imaged: 1 / Number real images: 7536 / Average exposure time: 5.9 sec. / Average electron dose: 67.7 e/Å2 Details: Movies were collected at super-resolution using correlated double sampling, with a frame time of 0.05 seconds and dose rate 8 e-/px/s |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.5 µm / Nominal magnification: 105000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |