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- EMDB-22660: SARS-CoV-2 spike in complex with the S2E12 neutralizing antibody ... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-22660 | |||||||||
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Title | SARS-CoV-2 spike in complex with the S2E12 neutralizing antibody Fab fragment (local refinement of the RBD and Fab variable domains) | |||||||||
![]() | Sharpened map | |||||||||
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![]() | SARS-CoV-2 / COVID-19 / spike glycoprotein / fusion protein / neutralizing antibodies / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID | |||||||||
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 / 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 | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.7 Å | |||||||||
![]() | Tortorici MA / Veesler D / Seattle Structural Genomics Center for Infectious Disease (SSGCID) | |||||||||
Funding support | 1 items
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![]() | ![]() Title: Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms. Authors: M Alejandra Tortorici / Martina Beltramello / Florian A Lempp / Dora Pinto / Ha V Dang / Laura E Rosen / Matthew McCallum / John Bowen / Andrea Minola / Stefano Jaconi / Fabrizia Zatta / ...Authors: M Alejandra Tortorici / Martina Beltramello / Florian A Lempp / Dora Pinto / Ha V Dang / Laura E Rosen / Matthew McCallum / John Bowen / Andrea Minola / Stefano Jaconi / Fabrizia Zatta / Anna De Marco / Barbara Guarino / Siro Bianchi / Elvin J Lauron / Heather Tucker / Jiayi Zhou / Alessia Peter / Colin Havenar-Daughton / Jason A Wojcechowskyj / James Brett Case / Rita E Chen / Hannah Kaiser / Martin Montiel-Ruiz / Marcel Meury / Nadine Czudnochowski / Roberto Spreafico / Josh Dillen / Cindy Ng / Nicole Sprugasci / Katja Culap / Fabio Benigni / Rana Abdelnabi / Shi-Yan Caroline Foo / Michael A Schmid / Elisabetta Cameroni / Agostino Riva / Arianna Gabrieli / Massimo Galli / Matteo S Pizzuto / Johan Neyts / Michael S Diamond / Herbert W Virgin / Gyorgy Snell / Davide Corti / Katja Fink / David Veesler / ![]() ![]() ![]() ![]() ![]() Abstract: Efficient therapeutic options are needed to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has caused more than 922,000 fatalities as of 13 September 2020. We ...Efficient therapeutic options are needed to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has caused more than 922,000 fatalities as of 13 September 2020. We report the isolation and characterization of two ultrapotent SARS-CoV-2 human neutralizing antibodies (S2E12 and S2M11) that protect hamsters against SARS-CoV-2 challenge. Cryo-electron microscopy structures show that S2E12 and S2M11 competitively block angiotensin-converting enzyme 2 (ACE2) attachment and that S2M11 also locks the spike in a closed conformation by recognition of a quaternary epitope spanning two adjacent receptor-binding domains. Antibody cocktails that include S2M11, S2E12, or the previously identified S309 antibody broadly neutralize a panel of circulating SARS-CoV-2 isolates and activate effector functions. Our results pave the way to implement antibody cocktails for prophylaxis or therapy, circumventing or limiting the emergence of viral escape mutants. | |||||||||
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 | ![]() | 922 KB | ![]() | |
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Header (meta data) | ![]() ![]() | 21.9 KB 21.9 KB | Display Display | ![]() |
Images | ![]() | 25.5 KB | ||
Filedesc metadata | ![]() | 7 KB | ||
Others | ![]() ![]() ![]() | 256.1 MB 475.1 MB 475 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7k45MC ![]() 7k3qC ![]() 7k43C ![]() 7k4nC 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
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Sharpened map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: Unsharpened map
File | emd_22660_additional_1.map | ||||||||||||
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Annotation | Unsharpened map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map B
File | emd_22660_half_map_1.map | ||||||||||||
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Annotation | Half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map A
File | emd_22660_half_map_2.map | ||||||||||||
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Annotation | Half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : SARS-CoV-2 spike in complex with the S2E12 neutralizing antibody ...
Entire | Name: SARS-CoV-2 spike in complex with the S2E12 neutralizing antibody Fab fragment |
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Components |
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-Supramolecule #1: SARS-CoV-2 spike in complex with the S2E12 neutralizing antibody ...
Supramolecule | Name: SARS-CoV-2 spike in complex with the S2E12 neutralizing antibody Fab fragment type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: S2E12 neutralizing antibody Fab fragment (heavy chain)
Macromolecule | Name: S2E12 neutralizing antibody Fab fragment (heavy chain) type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 13.420944 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: QVQLVQSGPE VKKPGTSVRV SCKASGFTFT SSAVQWVRQA RGQRLEWVGW IVVGSGNTNY AQKFHERVTI TRDMSTSTAY MELSSLRSE DTAVYYCASP YCSGGSCSDG FDIWGQGTMV TVSS |
-Macromolecule #2: S2E12 neutralizing antibody Fab fragment (light chain)
Macromolecule | Name: S2E12 neutralizing antibody Fab fragment (light chain) type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 11.786104 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: DIVLTQTPGT LSLSPGERAT LSCRASQSVS SSYLAWYQQK PGQAPRLLIY GASSRATGIP DRFSGSGSGT DFTLTISRLE PEDFAVYYC QQYVGLTGWT FGQGTKVEIK |
-Macromolecule #3: Spike glycoprotein
Macromolecule | Name: Spike glycoprotein / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 142.427438 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 KPSKRSPIED LLFNKVTLAD AGFIKQYGDC LGDIAARDLI CAQKFNGLTV LPPLLTDEMI AQYTSALLAG TITSGWTFG AGPALQIPFP MQMAYRFNGI GVTQNVLYEN QKLIANQFNS AIGKIQDSLS STPSALGKLQ 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 HHSAWSHPQF EKGGGSGGGG SGGSA WSHP QFEK UniProtKB: Spike glycoprotein |
-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: 8 |
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Grid | Model: UltrAuFoil R2/2 / Material: GOLD / Mesh: 200 |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 70.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: OTHER / Details: ab initio |
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Final reconstruction | Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.7 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 69829 |
Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |