+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-24262 | |||||||||
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Title | CryoEM structure of SARS-CoV-2 Spike in complex with Nb17 | |||||||||
Map data | ||||||||||
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 / Lama glama (llama) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.18 Å | |||||||||
Authors | Huang W / Taylor D | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Nat Commun / Year: 2021 Title: Potent neutralizing nanobodies resist convergent circulating variants of SARS-CoV-2 by targeting diverse and conserved epitopes. Authors: Dapeng Sun / Zhe Sang / Yong Joon Kim / Yufei Xiang / Tomer Cohen / Anna K Belford / Alexis Huet / James F Conway / Ji Sun / Derek J Taylor / Dina Schneidman-Duhovny / Cheng Zhang / Wei Huang / Yi Shi / Abstract: Interventions against variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed. Stable and potent nanobodies (Nbs) that target the receptor binding domain (RBD) of ...Interventions against variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed. Stable and potent nanobodies (Nbs) that target the receptor binding domain (RBD) of SARS-CoV-2 spike are promising therapeutics. However, it is unknown if Nbs broadly neutralize circulating variants. We found that RBD Nbs are highly resistant to variants of concern (VOCs). High-resolution cryoelectron microscopy determination of eight Nb-bound structures reveals multiple potent neutralizing epitopes clustered into three classes: Class I targets ACE2-binding sites and disrupts host receptor binding. Class II binds highly conserved epitopes and retains activity against VOCs and RBD. Cass III recognizes unique epitopes that are likely inaccessible to antibodies. Systematic comparisons of neutralizing antibodies and Nbs provided insights into how Nbs target the spike to achieve high-affinity and broadly neutralizing activity. Structure-function analysis of Nbs indicates a variety of antiviral mechanisms. Our study may guide the rational design of pan-coronavirus vaccines and therapeutics. | |||||||||
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_24262.map.gz | 89.8 MB | EMDB map data format | |
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Header (meta data) | emd-24262-v30.xml emd-24262.xml | 15.9 KB 15.9 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_24262_fsc.xml | 12.6 KB | Display | FSC data file |
Images | emd_24262.png | 61 KB | ||
Others | emd_24262_half_map_1.map.gz emd_24262_half_map_2.map.gz | 165.3 MB 165.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-24262 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-24262 | HTTPS FTP |
-Validation report
Summary document | emd_24262_validation.pdf.gz | 988.7 KB | Display | EMDB validaton report |
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Full document | emd_24262_full_validation.pdf.gz | 988.3 KB | Display | |
Data in XML | emd_24262_validation.xml.gz | 20.9 KB | Display | |
Data in CIF | emd_24262_validation.cif.gz | 26.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24262 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24262 | HTTPS FTP |
-Related structure data
Related structure data | 7n9tMC 7mdwC 7me7C 7mejC 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_24262.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.07 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Half map: #2
File | emd_24262_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_24262_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : SARS-CoV-2 S protein in complex with Nb17
Entire | Name: SARS-CoV-2 S protein in complex with Nb17 |
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Components |
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-Supramolecule #1: SARS-CoV-2 S protein in complex with Nb17
Supramolecule | Name: SARS-CoV-2 S protein in complex with Nb17 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Recombinant expression | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) |
-Macromolecule #1: Spike glycoprotein
Macromolecule | Name: Spike glycoprotein / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 124.190492 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: PPAYTNSFTR GVYYPDKVFR SSVLHSTQDL FLPFFSNVTW FHAIHVSGTN GTKRFDNPVL PFNDGVYFAS TEKSNIIRGW IFGTTLDSK TQSLLIVNNA TNVVIKVCEF QFCNDPFLGV YYHKNNKSWM ESEFRVYSSA NNCTFEYVSQ PFLMDLEGKQ G NFKNLREF ...String: PPAYTNSFTR GVYYPDKVFR SSVLHSTQDL FLPFFSNVTW FHAIHVSGTN GTKRFDNPVL PFNDGVYFAS TEKSNIIRGW IFGTTLDSK TQSLLIVNNA TNVVIKVCEF QFCNDPFLGV YYHKNNKSWM ESEFRVYSSA NNCTFEYVSQ PFLMDLEGKQ G NFKNLREF VFKNIDGYFK IYSKHTPINL VRDLPQGFSA LEPLVDLPIG INITRFQTLL ALHRSYLTPG DSSSGWTAGA AA YYVGYLQ PRTFLLKYNE NGTITDAVDC ALDPLSETKC TLKSFTVEKG IYQTSNFRVQ PTESIVRFPN ITNLCPFGEV FNA TRFASV YAWNRKRISN CVADYSVLYN SASFSTFKCY GVSPTKLNDL CFTNVYADSF VIRGDEVRQI APGQTGKIAD YNYK LPDDF TGCVIAWNSN NLDSKVGGNY NYLYRLFRKS NLKPFERDIS TEIYQAGSTP CNGVEGFNCY FPLQSYGFQP TNGVG YQPY RVVVLSFELL HAPATVCGPK KSTNLVKNKC VNFNFNGLTG TGVLTESNKK FLPFQQFGRD IADTTDAVRD PQTLEI LDI TPCSFGGVSV ITPGTNTSNQ VAVLYQDVNC TEVPVAIHAD QLTPTWRVYS TGSNVFQTRA GCLIGAEHVN NSYECDI PI GAGICASYQT QTNSPGSASS VASQSIIAYT MSLGAENSVA YSNNSIAIPT NFTISVTTEI LPVSMTKTSV DCTMYICG D STECSNLLLQ YGSFCTQLNR ALTGIAVEQD KNTQEVFAQV KQIYKTPPIK DFGGFNFSQI LPDPSKPSKR SFIEDLLFN KVTLADAGFI MQYGDCLGDM AYRDLICAQK FNGLTVLPPL LTDEMIAQYT SALLAGTITS GWTFGAGAAL QIPFAMQMAY RFNGIGVTQ NVLYENQKLI ANQFNSAIGK IQDSLSSTAS ALGKLQDVVN QNAQALNTLV KQLSSNFGAI SSVLNDILSR L DPPEAEVQ IDRLITGRLQ SLQTYVTQQL IRAAEIRASA NLAATKMSEC VLGQSKRVDF CGKGYHLMSF PQSAPHGVVF LH VTYVPAQ EKNFTTAPAI CHDGKAHFPR EGVFVSNGTH WFVTQRNFYE PQIITTDNTF VSGNCDVVIG IVNNTVYDPL QPE LDS |
-Macromolecule #2: Nanobody Nb17
Macromolecule | Name: Nanobody Nb17 / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Lama glama (llama) |
Molecular weight | Theoretical: 12.54084 KDa |
Recombinant expression | Organism: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) |
Sequence | String: HVQLVESGGG LVQAGGSLRL SCAASGSIFS SNAMSWYRQA PGKQRELVAS ITSGGNADYA DSVKGRFTIS RDKNTVYPEM SSLKPADTA VYYCHAVGQE ASAYAPRAYW GQGTQVTVSS |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Sugar embedding | Material: vitrified ice |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / 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 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |