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Yorodumi- EMDB-24365: SARS-CoV-2 S bound to S2X259 Fab (local refinement of the RBD/S2X... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-24365 | |||||||||
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Title | SARS-CoV-2 S bound to S2X259 Fab (local refinement of the RBD/S2X259 variable domains) | |||||||||
Map data | Sharpened map | |||||||||
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 | Homo sapiens (human) / Severe acute respiratory syndrome coronavirus 2 | |||||||||
Method | single particle reconstruction / cryo EM | |||||||||
Authors | Veesler D / Tortorici MA / Seattle Structural Genomics Center for Infectious Disease (SSGCID) | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Nature / Year: 2021 Title: Broad sarbecovirus neutralization by a human monoclonal antibody. Authors: M Alejandra Tortorici / Nadine Czudnochowski / Tyler N Starr / Roberta Marzi / Alexandra C Walls / Fabrizia Zatta / John E Bowen / Stefano Jaconi / Julia Di Iulio / Zhaoqian Wang / Anna De ...Authors: M Alejandra Tortorici / Nadine Czudnochowski / Tyler N Starr / Roberta Marzi / Alexandra C Walls / Fabrizia Zatta / John E Bowen / Stefano Jaconi / Julia Di Iulio / Zhaoqian Wang / Anna De Marco / Samantha K Zepeda / Dora Pinto / Zhuoming Liu / Martina Beltramello / Istvan Bartha / Michael P Housley / Florian A Lempp / Laura E Rosen / Exequiel Dellota / Hannah Kaiser / Martin Montiel-Ruiz / Jiayi Zhou / Amin Addetia / Barbara Guarino / Katja Culap / Nicole Sprugasci / Christian Saliba / Eneida Vetti / Isabella Giacchetto-Sasselli / Chiara Silacci Fregni / Rana Abdelnabi / Shi-Yan Caroline Foo / Colin Havenar-Daughton / Michael A Schmid / Fabio Benigni / Elisabetta Cameroni / Johan Neyts / Amalio Telenti / Herbert W Virgin / Sean P J Whelan / Gyorgy Snell / Jesse D Bloom / Davide Corti / David Veesler / Matteo Samuele Pizzuto / Abstract: The recent emergence of SARS-CoV-2 variants of concern and the recurrent spillovers of coronaviruses into the human population highlight the need for broadly neutralizing antibodies that are not ...The recent emergence of SARS-CoV-2 variants of concern and the recurrent spillovers of coronaviruses into the human population highlight the need for broadly neutralizing antibodies that are not affected by the ongoing antigenic drift and that can prevent or treat future zoonotic infections. Here we describe a human monoclonal antibody designated S2X259, which recognizes a highly conserved cryptic epitope of the receptor-binding domain and cross-reacts with spikes from all clades of sarbecovirus. S2X259 broadly neutralizes spike-mediated cell entry of SARS-CoV-2, including variants of concern (B.1.1.7, B.1.351, P.1, and B.1.427/B.1.429), as well as a wide spectrum of human and potentially zoonotic sarbecoviruses through inhibition of angiotensin-converting enzyme 2 (ACE2) binding to the receptor-binding domain. Furthermore, deep-mutational scanning and in vitro escape selection experiments demonstrate that S2X259 possesses an escape profile that is limited to a single substitution, G504D. We show that prophylactic and therapeutic administration of S2X259 protects Syrian hamsters (Mesocricetus auratus) against challenge with the prototypic SARS-CoV-2 and the B.1.351 variant of concern, which suggests that this monoclonal antibody is a promising candidate for the prevention and treatment of emergent variants and zoonotic infections. Our data reveal a key antigenic site that is targeted by broadly neutralizing antibodies and will guide the design of vaccines that are effective against all sarbecoviruses. | |||||||||
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_24365.map.gz | 730 KB | EMDB map data format | |
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Header (meta data) | emd-24365-v30.xml emd-24365.xml | 22.7 KB 22.7 KB | Display Display | EMDB header |
Images | emd_24365.png | 55.4 KB | ||
Others | emd_24365_additional_1.map.gz emd_24365_half_map_1.map.gz emd_24365_half_map_2.map.gz | 121.7 MB 226.5 MB 226.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-24365 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-24365 | HTTPS FTP |
-Validation report
Summary document | emd_24365_validation.pdf.gz | 711.6 KB | Display | EMDB validaton report |
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Full document | emd_24365_full_validation.pdf.gz | 711.2 KB | Display | |
Data in XML | emd_24365_validation.xml.gz | 8.7 KB | Display | |
Data in CIF | emd_24365_validation.cif.gz | 7.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24365 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24365 | HTTPS FTP |
-Related structure data
Related structure data | 7ralMC 7ra8C 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_24365.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Sharpened map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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_24365_additional_1.map | ||||||||||||
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Annotation | Unsharpened map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map A
File | emd_24365_half_map_1.map | ||||||||||||
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Annotation | Half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map B
File | emd_24365_half_map_2.map | ||||||||||||
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Annotation | Half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Severe acute respiratory syndrome coronavirus 2
Entire | Name: Severe acute respiratory syndrome coronavirus 2 |
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Components |
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-Supramolecule #1: Severe acute respiratory syndrome coronavirus 2
Supramolecule | Name: Severe acute respiratory syndrome coronavirus 2 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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-Supramolecule #2: S2X259 Fab
Supramolecule | Name: S2X259 Fab / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
-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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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Recombinant expression | Organism: Homo sapiens (human) |
-Macromolecule #1: S2X259 Fab heavy chain
Macromolecule | Name: S2X259 Fab heavy chain / 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: 13.755396 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLVQSGAE VKKPGSSVKV SCKASGGIFN TYTISWVRQA PGQGLEWMGR IILMSGMANY AQKIQGRVTI TADKSTSTAY MELTSLRSD DTAVYYCARG FNGNYYGWGD DDAFDIWGQG TLVTVYS |
-Macromolecule #2: S2X259 Fab light chain
Macromolecule | Name: S2X259 Fab light 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: 11.706813 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QTVLTQPPSV SGAPGQRVTI SCTGSNSNIG AGYDVHWYQQ LPGTAPKLLI CGNSNRPSGV PDRFSGSKSG TSASLAITGL QAEDEADYY CQSYDSSLSG PNWVFGGGTK LTVL |
-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: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 142.427438 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
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 |
-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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Sugar embedding | Material: Tris buffer saline |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 70.0 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
Final reconstruction | Number images used: 223152 |
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Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |