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Yorodumi- EMDB-23490: Cryo-EM structure of NTD-directed neutralizing antibody 2-17 Fab ... -
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-Basic information
Entry | Database: EMDB / ID: EMD-23490 | |||||||||
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Title | Cryo-EM structure of NTD-directed neutralizing antibody 2-17 Fab in complex with SARS-CoV-2 S2P spike | |||||||||
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 / membrane fusion / receptor-mediated endocytosis of virus by host cell / 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 | Severe acute respiratory syndrome coronavirus 2 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.47 Å | |||||||||
Authors | Gorman J / Rapp M / Kwong PD / Shapiro L | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Cell Host Microbe / Year: 2021 Title: Potent SARS-CoV-2 neutralizing antibodies directed against spike N-terminal domain target a single supersite. Authors: Gabriele Cerutti / Yicheng Guo / Tongqing Zhou / Jason Gorman / Myungjin Lee / Micah Rapp / Eswar R Reddem / Jian Yu / Fabiana Bahna / Jude Bimela / Yaoxing Huang / Phinikoula S Katsamba / ...Authors: Gabriele Cerutti / Yicheng Guo / Tongqing Zhou / Jason Gorman / Myungjin Lee / Micah Rapp / Eswar R Reddem / Jian Yu / Fabiana Bahna / Jude Bimela / Yaoxing Huang / Phinikoula S Katsamba / Lihong Liu / Manoj S Nair / Reda Rawi / Adam S Olia / Pengfei Wang / Baoshan Zhang / Gwo-Yu Chuang / David D Ho / Zizhang Sheng / Peter D Kwong / Lawrence Shapiro / Abstract: Numerous antibodies that neutralize SARS-CoV-2 have been identified, and these generally target either the receptor-binding domain (RBD) or the N-terminal domain (NTD) of the viral spike. While RBD- ...Numerous antibodies that neutralize SARS-CoV-2 have been identified, and these generally target either the receptor-binding domain (RBD) or the N-terminal domain (NTD) of the viral spike. While RBD-directed antibodies have been extensively studied, far less is known about NTD-directed antibodies. Here, we report cryo-EM and crystal structures for seven potent NTD-directed neutralizing antibodies in complex with spike or isolated NTD. These structures defined several antibody classes, with at least one observed in multiple convalescent donors. The structures revealed that all seven antibodies target a common surface, bordered by glycans N17, N74, N122, and N149. This site-formed primarily by a mobile β-hairpin and several flexible loops-was highly electropositive, located at the periphery of the spike, and the largest glycan-free surface of NTD facing away from the viral membrane. Thus, in contrast to neutralizing RBD-directed antibodies that recognize multiple non-overlapping epitopes, potent NTD-directed neutralizing antibodies appear to target a single supersite. | |||||||||
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_23490.map.gz | 230 MB | EMDB map data format | |
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Header (meta data) | emd-23490-v30.xml emd-23490.xml | 29.7 KB 29.7 KB | Display Display | EMDB header |
Images | emd_23490.png | 108.2 KB | ||
Masks | emd_23490_msk_1.map | 244.1 MB | Mask map | |
Others | emd_23490_additional_1.map.gz emd_23490_additional_2.map.gz emd_23490_additional_3.map.gz emd_23490_additional_4.map.gz emd_23490_additional_5.map.gz emd_23490_half_map_1.map.gz emd_23490_half_map_2.map.gz | 230.1 MB 121.1 MB 120.4 MB 41.5 MB 1.7 MB 226.2 MB 226.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-23490 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-23490 | HTTPS FTP |
-Validation report
Summary document | emd_23490_validation.pdf.gz | 1019.7 KB | Display | EMDB validaton report |
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Full document | emd_23490_full_validation.pdf.gz | 1019.2 KB | Display | |
Data in XML | emd_23490_validation.xml.gz | 16.2 KB | Display | |
Data in CIF | emd_23490_validation.cif.gz | 19.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23490 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23490 | HTTPS FTP |
-Related structure data
Related structure data | 7lqwMC 7l2cC 7l2dC 7l2eC 7l2fC 7lqvC C: citing same article (ref.) M: atomic model generated by this map |
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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_23490.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: 1.058 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_23490_msk_1.map | ||||||||||||
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-Additional map: Local sharpened map
File | emd_23490_additional_1.map | ||||||||||||
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Annotation | Local sharpened map | ||||||||||||
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-Additional map: unsharpened map
File | emd_23490_additional_2.map | ||||||||||||
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Annotation | unsharpened map | ||||||||||||
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-Additional map: #1
File | emd_23490_additional_3.map | ||||||||||||
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Density Histograms |
-Additional map: Full map density modified with resolve
File | emd_23490_additional_4.map | ||||||||||||
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Annotation | Full map density modified with resolve | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Local refinement density modified with resolve
File | emd_23490_additional_5.map | ||||||||||||
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Annotation | Local refinement density modified with resolve | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_23490_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_23490_half_map_2.map | ||||||||||||
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Density Histograms |
-Sample components
-Entire : 2-17 Fab in complex with SARS-CoV-2 S2P spike
Entire | Name: 2-17 Fab in complex with SARS-CoV-2 S2P spike |
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Components |
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-Supramolecule #1: 2-17 Fab in complex with SARS-CoV-2 S2P spike
Supramolecule | Name: 2-17 Fab in complex with SARS-CoV-2 S2P spike / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
-Macromolecule #1: 2-17 Heavy Chain
Macromolecule | Name: 2-17 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: 24.329279 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLVQSGAE VKKPGSSVKV SCKASGGTFS SYAISWVRQA PGQGLEWMGG NIPIFGTANY AQKFQGRVTI TADESTSTAY MELSSLRSE DTAVYYCARG VGYRGVIPLN WFDPWGQGTV VTVSSASTKG PSVFPLAPSS KSTSGGTAAL GCLVKDYFPE P VTVSWNSG ...String: QVQLVQSGAE VKKPGSSVKV SCKASGGTFS SYAISWVRQA PGQGLEWMGG NIPIFGTANY AQKFQGRVTI TADESTSTAY MELSSLRSE DTAVYYCARG VGYRGVIPLN WFDPWGQGTV VTVSSASTKG PSVFPLAPSS KSTSGGTAAL GCLVKDYFPE P VTVSWNSG ALTSGVHTFP AVLQSSGLYS LSSVVTVPSS SLGTQTYICN VNHKPSNTKV DKKVEPKSCD KTH |
-Macromolecule #2: 2-17 Light Chain
Macromolecule | Name: 2-17 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: 23.441014 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EIVMTQSPAT LSVSPGERAT LSCRASQSVS SDLAWYQHKP GQAPRLLIYG ASTRATGIPV RFSGSGSGTE FTLTISSLQS EDFAVYYCQ QYNNWPPFTF GGGTKVEIKR TVAAPSVFIF PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD ...String: EIVMTQSPAT LSVSPGERAT LSCRASQSVS SDLAWYQHKP GQAPRLLIYG ASTRATGIPV RFSGSGSGTE FTLTISSLQS EDFAVYYCQ QYNNWPPFTF GGGTKVEIKR TVAAPSVFIF PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD SKDSTYSLSS TLTLSKADYE KHKVYACEVT HQGLSSPVTK SFNRGEC |
-Macromolecule #3: Spike glycoprotein
Macromolecule | Name: Spike glycoprotein / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 144.106422 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MGILPSPGMP ALLSLVSLLS VLLMGCVAET GTQCVNLTTR TQLPPAYTNS FTRGVYYPDK VFRSSVLHST QDLFLPFFSN VTWFHAIHV SGTNGTKRFD NPVLPFNDGV YFASTEKSNI IRGWIFGTTL DSKTQSLLIV NNATNVVIKV CEFQFCNDPF L GVYYHKNN ...String: MGILPSPGMP ALLSLVSLLS VLLMGCVAET GTQCVNLTTR TQLPPAYTNS FTRGVYYPDK VFRSSVLHST QDLFLPFFSN VTWFHAIHV SGTNGTKRFD NPVLPFNDGV YFASTEKSNI IRGWIFGTTL DSKTQSLLIV NNATNVVIKV CEFQFCNDPF L GVYYHKNN KSWMESEFRV YSSANNCTFE YVSQPFLMDL EGKQGNFKNL REFVFKNIDG YFKIYSKHTP INLVRDLPQG FS ALEPLVD LPIGINITRF QTLLALHRSY LTPGDSSSGW TAGAAAYYVG YLQPRTFLLK YNENGTITDA VDCALDPLSE TKC TLKSFT VEKGIYQTSN FRVQPTESIV RFPNITNLCP FGEVFNATRF ASVYAWNRKR ISNCVADYSV LYNSASFSTF KCYG VSPTK LNDLCFTNVY ADSFVIRGDE VRQIAPGQTG KIADYNYKLP DDFTGCVIAW NSNNLDSKVG GNYNYLYRLF RKSNL KPFE RDISTEIYQA GSTPCNGVEG FNCYFPLQSY GFQPTNGVGY QPYRVVVLSF ELLHAPATVC GPKKSTNLVK NKCVNF NFN GLTGTGVLTE SNKKFLPFQQ FGRDIADTTD AVRDPQTLEI LDITPCSFGG VSVITPGTNT SNQVAVLYQD VNCTEVP VA IHADQLTPTW RVYSTGSNVF QTRAGCLIGA EHVNNSYECD IPIGAGICAS YQTQTNSPGS ASSVASQSII AYTMSLGA E NSVAYSNNSI AIPTNFTISV TTEILPVSMT KTSVDCTMYI CGDSTECSNL LLQYGSFCTQ LNRALTGIAV EQDKNTQEV FAQVKQIYKT PPIKDFGGFN FSQILPDPSK PSKRSFIEDL LFNKVTLADA GFIKQYGDCL GDIAARDLIC AQKFNGLTVL PPLLTDEMI AQYTSALLAG TITSGWTFGA GAALQIPFAM QMAYRFNGIG VTQNVLYENQ KLIANQFNSA IGKIQDSLSS T ASALGKLQ DVVNQNAQAL NTLVKQLSSN FGAISSVLND ILSRLDPPEA EVQIDRLITG RLQSLQTYVT QQLIRAAEIR AS ANLAATK MSECVLGQSK RVDFCGKGYH LMSFPQSAPH GVVFLHVTYV PAQEKNFTTA PAICHDGKAH FPREGVFVSN GTH WFVTQR NFYEPQIITT DNTFVSGNCD VVIGIVNNTV YDPLQPELDS FKEELDKYFK NHTSPDVDLG DISGINASVV NIQK EIDRL NEVAKNLNES LIDLQELGKY EQGSGYIPEA PRDGQAYVRK DGEWVLLSTF LGRSLEVLFQ GPGHHHHHHH HSAWS HPQF EKGGGSGGGG SGGSAWSHPQ FEK |
-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: 26 / 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
Concentration | 1 mg/mL |
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Buffer | pH: 5.5 / Component - Formula: PBS |
Grid | Model: C-flat-1.2/1.3 / Material: COPPER |
Vitrification | Cryogen name: ETHANE |
Details | PBS with sodium acetate, pH 5.5 |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 51.69 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
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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Final reconstruction | Applied symmetry - Point group: C1 (asymmetric) / Algorithm: FOURIER SPACE / Resolution.type: BY AUTHOR / Resolution: 4.47 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 29767 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
-Atomic model buiding 1
Refinement | Protocol: FLEXIBLE FIT |
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Output model | PDB-7lqw: |