+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-26401 | |||||||||
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Title | SARS-CoV-2 spike trimer in complex with Fab NE12, ensemble map | |||||||||
Map data | Map after post-processing | |||||||||
Sample |
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Biological species | Severe acute respiratory syndrome coronavirus 2 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
Authors | Tsybovsky Y / Kwong PD / Farci P | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Cell Rep / Year: 2022 Title: Potent monoclonal antibodies neutralize Omicron sublineages and other SARS-CoV-2 variants. Authors: Zhaochun Chen / Peng Zhang / Yumiko Matsuoka / Yaroslav Tsybovsky / Kamille West / Celia Santos / Lisa F Boyd / Hanh Nguyen / Anna Pomerenke / Tyler Stephens / Adam S Olia / Baoshan Zhang / ...Authors: Zhaochun Chen / Peng Zhang / Yumiko Matsuoka / Yaroslav Tsybovsky / Kamille West / Celia Santos / Lisa F Boyd / Hanh Nguyen / Anna Pomerenke / Tyler Stephens / Adam S Olia / Baoshan Zhang / Valeria De Giorgi / Michael R Holbrook / Robin Gross / Elena Postnikova / Nicole L Garza / Reed F Johnson / David H Margulies / Peter D Kwong / Harvey J Alter / Ursula J Buchholz / Paolo Lusso / Patrizia Farci / Abstract: The emergence and global spread of the SARS-CoV-2 Omicron variants, which carry an unprecedented number of mutations, raise serious concerns due to the reduced efficacy of current vaccines and ...The emergence and global spread of the SARS-CoV-2 Omicron variants, which carry an unprecedented number of mutations, raise serious concerns due to the reduced efficacy of current vaccines and resistance to therapeutic antibodies. Here, we report the generation and characterization of two potent human monoclonal antibodies, NA8 and NE12, against the receptor-binding domain of the SARS-CoV-2 spike protein. NA8 interacts with a highly conserved region and has a breadth of neutralization with picomolar potency against the Beta variant and the Omicron BA.1 and BA.2 sublineages and nanomolar potency against BA.2.12.1 and BA.4. Combination of NA8 and NE12 retains potent neutralizing activity against the major SARS-CoV-2 variants of concern. Cryo-EM analysis provides the structural basis for the broad and complementary neutralizing activity of these two antibodies. We confirm the in vivo protective and therapeutic efficacies of NA8 and NE12 in the hamster model. These results show that broad and potent human antibodies can overcome the continuous immune escape of evolving SARS-CoV-2 variants. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_26401.map.gz | 27.1 MB | EMDB map data format | |
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Header (meta data) | emd-26401-v30.xml emd-26401.xml | 21.9 KB 21.9 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_26401_fsc.xml | 16.3 KB | Display | FSC data file |
Images | emd_26401.png | 55.7 KB | ||
Masks | emd_26401_msk_1.map | 371.3 MB | Mask map | |
Others | emd_26401_additional_1.map.gz emd_26401_half_map_1.map.gz emd_26401_half_map_2.map.gz | 298.7 MB 299 MB 298.6 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-26401 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26401 | HTTPS FTP |
-Validation report
Summary document | emd_26401_validation.pdf.gz | 712.7 KB | Display | EMDB validaton report |
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Full document | emd_26401_full_validation.pdf.gz | 712.3 KB | Display | |
Data in XML | emd_26401_validation.xml.gz | 23.2 KB | Display | |
Data in CIF | emd_26401_validation.cif.gz | 30.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26401 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26401 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_26401.map.gz / Format: CCP4 / Size: 371.3 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | Map after post-processing | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.873 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_26401_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: Map before post-processing
File | emd_26401_additional_1.map | ||||||||||||
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Annotation | Map before post-processing | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half-map 2
File | emd_26401_half_map_1.map | ||||||||||||
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Annotation | Half-map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half-map 1
File | emd_26401_half_map_2.map | ||||||||||||
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Annotation | Half-map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : SARS-CoV-2 S6P spike trimer in complex with Fab NE12
Entire | Name: SARS-CoV-2 S6P spike trimer in complex with Fab NE12 |
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Components |
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-Supramolecule #1: SARS-CoV-2 S6P spike trimer in complex with Fab NE12
Supramolecule | Name: SARS-CoV-2 S6P spike trimer in complex with Fab NE12 / type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 580 KDa |
-Macromolecule #1: SARS-CoV-2 S6P spike trimer
Macromolecule | Name: SARS-CoV-2 S6P spike trimer / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QCVNLTTRTQ LPPAYTNSFT RGVYYPDKVF RSSVLHSTQD LFLPF FSNV TWFHAIHVSG TNGTKRFDNP VLPFNDGVYF ASTEKSNIIR GWIFGT TLD SKTQSLLIVN NATNVVIKVC EFQFCNDPFL GVYYHKNNKS WMESEFR VY SSANNCTFEY VSQPFLMDLE ...String: QCVNLTTRTQ LPPAYTNSFT RGVYYPDKVF RSSVLHSTQD LFLPF FSNV TWFHAIHVSG TNGTKRFDNP VLPFNDGVYF ASTEKSNIIR GWIFGT TLD SKTQSLLIVN NATNVVIKVC EFQFCNDPFL GVYYHKNNKS WMESEFR VY SSANNCTFEY VSQPFLMDLE GKQGNFKNLR EFVFKNIDGY FKIYSKHT P INLVRDLPQG FSALEPLVDL PIGINITRFQ TLLALHRSYL TPGDSSSGW TAGAAAYYVG YLQPRTFLLK YNENGTITDA VDCALDPLSE TKCTLKSFTV EKGIYQTSN FRVQPTESIV RFPNITNLCP FGEVFNATRF ASVYAWNRKR I SNCVADYS VLYNSASFST FKCYGVSPTK LNDLCFTNVY ADSFVIRGDE VR QIAPGQT GKIADYNYKL PDDFTGCVIA WNSNNLDSKV GGNYNYLYRL FRK SNLKPF ERDISTEIYQ AGSTPCNGVE GFNCYFPLQS YGFQPTNGVG YQPY RVVVL SFELLHAPAT VCGPKKSTNL VKNKCVNFNF NGLTGTGVLT ESNKK FLPF QQFGRDIADT TDAVRDPQTL EILDITPCSF GGVSVITPGT NTSNQV AVL YQDVNCTEVP VAIHADQLTP TWRVYSTGSN VFQTRAGCLI GAEHVNN SY ECDIPIGAGI CASYQTQTNS PGSASSVASQ SIIAYTMSLG AENSVAYS N NSIAIPTNFT ISVTTEILPV SMTKTSVDCT MYICGDSTEC SNLLLQYGS FCTQLNRALT GIAVEQDKNT QEVFAQVKQI YKTPPIKDFG GFNFSQILPD PSKPSKRSP IEDLLFNKVT LADAGFIKQY GDCLGDIAAR DLICAQKFNG L TVLPPLLT DEMIAQYTSA LLAGTITSGW TFGAGPALQI PFPMQMAYRF NG IGVTQNV LYENQKLIAN QFNSAIGKIQ DSLSSTPSAL GKLQDVVNQN AQA LNTLVK QLSSNFGAIS SVLNDILSRL DPPEAEVQID RLITGRLQSL QTYV TQQLI RAAEIRASAN LAATKMSECV LGQSKRVDFC GKGYHLMSFP QSAPH GVVF LHVTYVPAQE KNFTTAPAIC HDGKAHFPRE GVFVSNGTHW FVTQRN FYE PQIITTDNTF VSGNCDVVIG IVNNTVYDPL QPELDSFKEE LDKYFKN HT SPDVDLGDIS GINASVVNIQ KEIDRLNEVA KNLNESLIDL QELGKYEQ G SGYIPEAPRD GQAYVRKDGE WVLLSTFLGR SLEVLFQGPG HHHHHHHHS AWSHPQFEKG GGSGGGGSGG SAWSHPQFEK |
-Macromolecule #2: NE12 Fab heavy chain
Macromolecule | Name: NE12 Fab heavy chain / type: protein_or_peptide / ID: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: VQLLEQSGAE VKKPGASVKV SCKASGDTFT GYYMHWVRQA PGQGLEWMGW INPNSGVTNY AQKFQGWVT MTRDTSISTV YMELNRLRSD DTAVYYCARE ETIVGATPPY GLDVWGQGTT V TVSSASTK GPSVFPGAPS SKSTSGGTAA LGCLVKDYFP EPVTVSWNSG ...String: VQLLEQSGAE VKKPGASVKV SCKASGDTFT GYYMHWVRQA PGQGLEWMGW INPNSGVTNY AQKFQGWVT MTRDTSISTV YMELNRLRSD DTAVYYCARE ETIVGATPPY GLDVWGQGTT V TVSSASTK GPSVFPGAPS SKSTSGGTAA LGCLVKDYFP EPVTVSWNSG ALTSGVHTFP AV LQSSGLY SLSSVVTVPS SSLGTQTYIC NVDHKPATPR WTRKLSPNLV TKL |
-Macromolecule #3: NE12 Fab light chain
Macromolecule | Name: NE12 Fab light chain / type: protein_or_peptide / ID: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: ELVLTQSPAT LSLSPGERAT LSCRASQSVS SYLAWYQQKP GQAPRLLIYD ASNRATGI P ARFSGSGSGT DFTLTISSLE PEDFAVYYCQ QRSNWPPVTF GQGTRLEIKR TVAAPSVFI FPPSDEQLKS GTASVVCLLN NFYPREAKVQ WKVDNALQSG NSQESVTEQD ...String: ELVLTQSPAT LSLSPGERAT LSCRASQSVS SYLAWYQQKP GQAPRLLIYD ASNRATGI P ARFSGSGSGT DFTLTISSLE PEDFAVYYCQ QRSNWPPVTF GQGTRLEIKR TVAAPSVFI FPPSDEQLKS GTASVVCLLN NFYPREAKVQ WKVDNALQSG NSQESVTEQD SKDSTYSLSS TLTLSKADY EKHKVYACEV THQGLSSPVT KSFNRGEC |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 / Details: PBS |
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Grid | Model: Quantifoil R2/2 / Material: GOLD / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Atmosphere: AIR / Pretreatment - Pressure: 0.039 kPa |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Number grids imaged: 1 / Average electron dose: 40.0 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 / 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 |
+Image processing
-Atomic model buiding 1
Initial model | PDB ID: |
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Refinement | Space: REAL / Protocol: BACKBONE TRACE |