+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-27177 | |||||||||
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Title | sd1.040 Fab in complex with SARS-CoV-2 Spike 2P glycoprotein | |||||||||
Map data | sd1.040 Fab in complex with SARS-CoV-2 Spike 2P glycoprotein | |||||||||
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 / 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: 3.7 Å | |||||||||
Authors | Abernathy ME / Barnes CO | |||||||||
Funding support | United States, 1 items
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Citation | Journal: bioRxiv / Year: 2022 Title: Human neutralizing antibodies to cold linear epitopes and to subdomain 1 of SARS-CoV-2. Authors: Filippo Bianchini / Virginia Crivelli / Morgan E Abernathy / Concetta Guerra / Martin Palus / Jonathan Muri / Harold Marcotte / Antonio Piralla / Mattia Pedotti / Raoul De Gasparo / Luca ...Authors: Filippo Bianchini / Virginia Crivelli / Morgan E Abernathy / Concetta Guerra / Martin Palus / Jonathan Muri / Harold Marcotte / Antonio Piralla / Mattia Pedotti / Raoul De Gasparo / Luca Simonelli / Milos Matkovic / Chiara Toscano / Maira Biggiogero / Veronica Calvaruso / Pavel Svoboda / Tomás Cervantes Rincón / Tommaso Fava / Lucie Podešvová / Akanksha A Shanbhag / Andrea Celoria / Jacopo Sgrignani / Michal Stefanik / Vaclav Hönig / Veronika Pranclova / Tereza Michalcikova / Jan Prochazka / Giuditta Guerrini / Dora Mehn / Annalisa Ciabattini / Hassan Abolhassani / David Jarrossay / Mariagrazia Uguccioni / Donata Medaglini / Qiang Pan-Hammarström / Luigi Calzolai / Daniel Fernandez / Fausto Baldanti / Alessandra Franzetti-Pellanda / Christian Garzoni / Radislav Sedlacek / Daniel Ruzek / Luca Varani / Andrea Cavalli / Christopher O Barnes / Davide F Robbiani / Abstract: Emergence of SARS-CoV-2 variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution ...Emergence of SARS-CoV-2 variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions of the virus spike that are both functionally relevant and averse to change, we identified human neutralizing antibodies to highly conserved viral epitopes. Antibody fp.006 binds the fusion peptide and cross-reacts against coronaviruses of the four , including the nine human coronaviruses, through recognition of a conserved motif that includes the S2' site of proteolytic cleavage. Antibody hr2.016 targets the stem helix and neutralizes SARS-CoV-2 variants. Antibody sd1.040 binds to subdomain 1, synergizes with antibody rbd.042 for neutralization and, like fp.006 and hr2.016, protects mice when present as bispecific antibody. Thus, coldspot-guided antibody discovery reveals donor-derived neutralizing antibodies that are cross-reactive with , including SARS-CoV-2 variants. ONE SENTENCE SUMMARY: Broadly cross-reactive antibodies that protect from SARS-CoV-2 variants are revealed by virus coldspot-driven discovery. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_27177.map.gz | 290.2 MB | EMDB map data format | |
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Header (meta data) | emd-27177-v30.xml emd-27177.xml | 30.6 KB 30.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_27177_fsc.xml | 14.3 KB | Display | FSC data file |
Images | emd_27177.png | 21.2 KB | ||
Others | emd_27177_additional_1.map.gz emd_27177_half_map_1.map.gz emd_27177_half_map_2.map.gz | 153.6 MB 285.1 MB 285.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-27177 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-27177 | HTTPS FTP |
-Validation report
Summary document | emd_27177_validation.pdf.gz | 753.8 KB | Display | EMDB validaton report |
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Full document | emd_27177_full_validation.pdf.gz | 753.4 KB | Display | |
Data in XML | emd_27177_validation.xml.gz | 23.4 KB | Display | |
Data in CIF | emd_27177_validation.cif.gz | 30.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27177 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27177 | HTTPS FTP |
-Related structure data
Related structure data | 8d48MC 8d47C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_27177.map.gz / Format: CCP4 / Size: 307.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | sd1.040 Fab in complex with SARS-CoV-2 Spike 2P glycoprotein | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.8521 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: sd1.040 Fab in complex with SARS-CoV-2 Spike 2P glycoprotein
File | emd_27177_additional_1.map | ||||||||||||
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Annotation | sd1.040 Fab in complex with SARS-CoV-2 Spike 2P glycoprotein | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: sd1.040 Fab in complex with SARS-CoV-2 Spike 2P glycoprotein
File | emd_27177_half_map_1.map | ||||||||||||
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Annotation | sd1.040 Fab in complex with SARS-CoV-2 Spike 2P glycoprotein | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: sd1.040 Fab in complex with SARS-CoV-2 Spike 2P glycoprotein
File | emd_27177_half_map_2.map | ||||||||||||
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Annotation | sd1.040 Fab in complex with SARS-CoV-2 Spike 2P glycoprotein | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : sd1.040 Fab in complex with SARS-CoV-2 Spike 2P
Entire | Name: sd1.040 Fab in complex with SARS-CoV-2 Spike 2P |
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Components |
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-Supramolecule #1: sd1.040 Fab in complex with SARS-CoV-2 Spike 2P
Supramolecule | Name: sd1.040 Fab in complex with SARS-CoV-2 Spike 2P / type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: all |
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Molecular weight | Theoretical: 79 KDa |
-Supramolecule #2: Spike glycoprotein
Supramolecule | Name: Spike glycoprotein / type: complex / ID: 2 / Chimera: Yes / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
-Supramolecule #3: sd1.040 Fab heavy chain, sd1.040 Fab light chain
Supramolecule | Name: sd1.040 Fab heavy chain, sd1.040 Fab light chain / type: complex / ID: 3 / Chimera: Yes / Parent: 1 / Macromolecule list: #2-#3 |
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Source (natural) | Organism: Homo sapiens (human) |
-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: 139.787969 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 SYQTQTNSPR RARSVASQSI 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 YEQYIKWPSG RLVPRGSPGS GYIPEAPRDG QAYVRKDGEW VLLSTFLGHH HHHH |
-Macromolecule #2: sd1.040 Fab heavy chain
Macromolecule | Name: sd1.040 Fab 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: 24.945762 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLVQSGAE VKKPGASVKV SCKASGYTFT SFYIHWVRQA PGQGLEWMGI IDPSGGSTSY PQKFQGRVTM TRDTSTSTVY MDLSSLRSE DTAVYYCTRD GSAGDNSWFD PWGQGTLVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL VKDYFPEPVT V SWNSGALT ...String: QVQLVQSGAE VKKPGASVKV SCKASGYTFT SFYIHWVRQA PGQGLEWMGI IDPSGGSTSY PQKFQGRVTM TRDTSTSTVY MDLSSLRSE DTAVYYCTRD GSAGDNSWFD PWGQGTLVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL VKDYFPEPVT V SWNSGALT SGVHTFPAVL QSSGLYSLSS VVTVPSSSLG TQTYICNVNH KPSNTKVDKR VEPKSCDKTH HHHHH |
-Macromolecule #3: sd1.040 Fab light chain
Macromolecule | Name: sd1.040 Fab 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: 24.346984 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DIVMTQSPDS LAVSLGERAT INCKSSRNVL YSSNNKNYLA WYQQKPGQPP KLLIYWASAR ESGVPDRFSG SGSGTDFTLT ISSLQAEDV AVYYCQQYYN TPYTFGQGTK LEIKRTVAAP SVFIFPPSDE QLKSGTASVV CLLNNFYPRE AKVQWKVDNA L QSGNSQES ...String: DIVMTQSPDS LAVSLGERAT INCKSSRNVL YSSNNKNYLA WYQQKPGQPP KLLIYWASAR ESGVPDRFSG SGSGTDFTLT ISSLQAEDV AVYYCQQYYN TPYTFGQGTK LEIKRTVAAP SVFIFPPSDE QLKSGTASVV CLLNNFYPRE AKVQWKVDNA L QSGNSQES VTEQDSKDST YSLSSTLTLS KADYEKHKVY ACEVTHQGLS SPVTKSFNRG EC |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 3 mg/mL | |||||||||
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Buffer | pH: 8 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 295 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | TFS 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) / Number grids imaged: 1 / Number real images: 9894 / Average exposure time: 2.88 sec. / Average electron dose: 59.3 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |