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- EMDB-12274: EM structure of SARS-CoV-2 Spike glycoprotein in complex with COV... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-12274 | |||||||||
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Title | EM structure of SARS-CoV-2 Spike glycoprotein in complex with COVOX-40 Fab | |||||||||
![]() | contour level 0.333 for better ordered regions | |||||||||
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![]() | SARS-CoV-2 / antibody / germline / V-gene / receptor-binding-domain / spike / neutralisation / protection / glycosylation / valency / VIRAL PROTEIN/IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
Function / homology | ![]() 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 | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.7 Å | |||||||||
![]() | Duyvesteyn HME / Zhao Y / Ren J / Stuart D | |||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: The antigenic anatomy of SARS-CoV-2 receptor binding domain. Authors: Wanwisa Dejnirattisai / Daming Zhou / Helen M Ginn / Helen M E Duyvesteyn / Piyada Supasa / James Brett Case / Yuguang Zhao / Thomas S Walter / Alexander J Mentzer / Chang Liu / Beibei Wang ...Authors: Wanwisa Dejnirattisai / Daming Zhou / Helen M Ginn / Helen M E Duyvesteyn / Piyada Supasa / James Brett Case / Yuguang Zhao / Thomas S Walter / Alexander J Mentzer / Chang Liu / Beibei Wang / Guido C Paesen / Jose Slon-Campos / César López-Camacho / Natasha M Kafai / Adam L Bailey / Rita E Chen / Baoling Ying / Craig Thompson / Jai Bolton / Alex Fyfe / Sunetra Gupta / Tiong Kit Tan / Javier Gilbert-Jaramillo / William James / Michael Knight / Miles W Carroll / Donal Skelly / Christina Dold / Yanchun Peng / Robert Levin / Tao Dong / Andrew J Pollard / Julian C Knight / Paul Klenerman / Nigel Temperton / David R Hall / Mark A Williams / Neil G Paterson / Felicity K R Bertram / C Alistair Siebert / Daniel K Clare / Andrew Howe / Julika Radecke / Yun Song / Alain R Townsend / Kuan-Ying A Huang / Elizabeth E Fry / Juthathip Mongkolsapaya / Michael S Diamond / Jingshan Ren / David I Stuart / Gavin R Screaton / ![]() ![]() ![]() ![]() Abstract: Antibodies are crucial to immune protection against SARS-CoV-2, with some in emergency use as therapeutics. Here, we identify 377 human monoclonal antibodies (mAbs) recognizing the virus spike and ...Antibodies are crucial to immune protection against SARS-CoV-2, with some in emergency use as therapeutics. Here, we identify 377 human monoclonal antibodies (mAbs) recognizing the virus spike and focus mainly on 80 that bind the receptor binding domain (RBD). We devise a competition data-driven method to map RBD binding sites. We find that although antibody binding sites are widely dispersed, neutralizing antibody binding is focused, with nearly all highly inhibitory mAbs (IC < 0.1 μg/mL) blocking receptor interaction, except for one that binds a unique epitope in the N-terminal domain. Many of these neutralizing mAbs use public V-genes and are close to germline. We dissect the structural basis of recognition for this large panel of antibodies through X-ray crystallography and cryoelectron microscopy of 19 Fab-antigen structures. We find novel binding modes for some potently inhibitory antibodies and demonstrate that strongly neutralizing mAbs protect, prophylactically or therapeutically, in animal models. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 13 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 20.2 KB 20.2 KB | Display Display | ![]() |
Images | ![]() | 277.8 KB | ||
Filedesc metadata | ![]() | 7.7 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 342.8 KB | Display | ![]() |
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Full document | ![]() | 342.3 KB | Display | |
Data in XML | ![]() | 7.8 KB | Display | |
Data in CIF | ![]() | 8.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7nd3MC ![]() 7behC ![]() 7beiC ![]() 7bejC ![]() 7bekC ![]() 7belC ![]() 7bemC ![]() 7benC ![]() 7beoC ![]() 7bepC ![]() 7nd4C ![]() 7nd5C ![]() 7nd6C ![]() 7nd7C ![]() 7nd8C ![]() 7nd9C ![]() 7ndaC ![]() 7ndbC ![]() 7ndcC ![]() 7nddC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | contour level 0.333 for better ordered regions | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.83 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : Complex of SARS-COV-2 spike glycoprotein with COVOX-40 Fab
Entire | Name: Complex of SARS-COV-2 spike glycoprotein with COVOX-40 Fab |
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Components |
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-Supramolecule #1: Complex of SARS-COV-2 spike glycoprotein with COVOX-40 Fab
Supramolecule | Name: Complex of SARS-COV-2 spike glycoprotein with COVOX-40 Fab type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Molecular weight | Theoretical: 488 KDa |
-Supramolecule #2: SARS-COV-2 spike glycoprotein
Supramolecule | Name: SARS-COV-2 spike glycoprotein / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() ![]() |
-Supramolecule #3: COVOX-40 Fab
Supramolecule | Name: COVOX-40 Fab / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Spike glycoprotein
Macromolecule | Name: Spike glycoprotein / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 142.399375 KDa |
Recombinant expression | Organism: ![]() |
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 YEQGSGYIPE APRDGQAYVR KDGEWVLLST FLGRSLEVLF QGPGHHHHHH HHGSAWSHPQ FEKGGGSGGG SGGSA WSHP QFEK UniProtKB: Spike glycoprotein |
-Macromolecule #2: COVOX-40 heavy chain
Macromolecule | Name: COVOX-40 heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 25.254402 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: ILFLVATATG VHSQVQLVES GGGLVQPGGS LRLSCAVSGF TVSRNYMSWV RQAPGKGLEW VSLIYSGGST FYADSVKGRF TISRDNSKN TLYLQMNSLR AEDTAVYYCA RDLFHRSGYH DYWGQGTLVT VSSASTKGPS VFPLAPSSKS TSGGTAALGC L VKDYFPEP ...String: ILFLVATATG VHSQVQLVES GGGLVQPGGS LRLSCAVSGF TVSRNYMSWV RQAPGKGLEW VSLIYSGGST FYADSVKGRF TISRDNSKN TLYLQMNSLR AEDTAVYYCA RDLFHRSGYH DYWGQGTLVT VSSASTKGPS VFPLAPSSKS TSGGTAALGC L VKDYFPEP VTVSWNSGAL TSGVHTFPAV LQSSGLYSLS SVVTVPSSSL GTQTYICNVN HKPSNTKVDK KVEPKSCDK |
-Macromolecule #3: COVOX-40 light chain
Macromolecule | Name: COVOX-40 light chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 24.615336 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: ILFLVATATG VHSVIWMTQS PSSLSASVGD RVTITCQASQ DINNYLNWYQ QKPGKAPKLL IFDASNLETG VPSRFSGSGS GTDFTFTIS SLQPEDIATY YCQQYDNLPA FGGGTKVDIK RTVAAPSVFI FPPSDEQLKS GTASVVCLLN NFYPREAKVQ W KVDNALQS ...String: ILFLVATATG VHSVIWMTQS PSSLSASVGD RVTITCQASQ DINNYLNWYQ QKPGKAPKLL IFDASNLETG VPSRFSGSGS GTDFTFTIS SLQPEDIATY YCQQYDNLPA FGGGTKVDIK RTVAAPSVFI FPPSDEQLKS GTASVVCLLN NFYPREAKVQ W KVDNALQS GNSQESVTEQ DSKDSTYSLS STLTLSKADY EKHKVYACEV THQGLSSPVT KSFNRGEC |
-Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 27 / 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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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Grid | Model: C-flat-2/1 / Material: COPPER / Mesh: 200 / Support film - Material: CARBON / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 20 sec. |
Vitrification | Cryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Slit width: 20 eV |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Detector mode: COUNTING / Number grids imaged: 1 / Number real images: 9622 / Average electron dose: 43.1 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: OTHER / Imaging mode: BRIGHT FIELD |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Initial model |
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Output model | ![]() PDB-7nd3: |