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Yorodumi- EMDB-28947: Cryo-EM structure of the SARS-CoV-2 HR1HR2 fusion core complex wi... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-28947 | |||||||||
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Title | Cryo-EM structure of the SARS-CoV-2 HR1HR2 fusion core complex with N969K mutation | |||||||||
Map data | ||||||||||
Sample |
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Keywords | spike / HR1HR2 / fusion / scaffold / VIRAL PROTEIN | |||||||||
Function / homology | Function and homology information oxidoreductase activity, acting on metal ions / ferric iron binding / endocytosis involved in viral entry into 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 ...oxidoreductase activity, acting on metal ions / ferric iron binding / endocytosis involved in viral entry into 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 / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / entry receptor-mediated virion attachment to host cell / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / membrane fusion / 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 | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.51 Å | |||||||||
Authors | Yang K / Brunger AT | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2023 Title: Structure-based design of a SARS-CoV-2 Omicron-specific inhibitor. Authors: Kailu Yang / Chuchu Wang / Alex J B Kreutzberger / K Ian White / Richard A Pfuetzner / Luis Esquivies / Tomas Kirchhausen / Axel T Brunger / Abstract: The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) introduced a relatively large number of mutations, including three mutations in the highly conserved heptad repeat ...The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) introduced a relatively large number of mutations, including three mutations in the highly conserved heptad repeat 1 (HR1) region of the spike glycoprotein (S) critical for its membrane fusion activity. We show that one of these mutations, N969K induces a substantial displacement in the structure of the heptad repeat 2 (HR2) backbone in the HR1HR2 postfusion bundle. Due to this mutation, fusion-entry peptide inhibitors based on the Wuhan strain sequence are less efficacious. Here, we report an Omicron-specific peptide inhibitor designed based on the structure of the Omicron HR1HR2 postfusion bundle. Specifically, we inserted an additional residue in HR2 near the Omicron HR1 K969 residue to better accommodate the N969K mutation and relieve the distortion in the structure of the HR1HR2 postfusion bundle it introduced. The designed inhibitor recovers the loss of inhibition activity of the original longHR2_42 peptide with the Wuhan strain sequence against the Omicron variant in both a cell-cell fusion assay and a vesicular stomatitis virus (VSV)-SARS-CoV-2 chimera infection assay, suggesting that a similar approach could be used to combat future variants. From a mechanistic perspective, our work suggests the interactions in the extended region of HR2 may mediate the initial landing of HR2 onto HR1 during the transition of the S protein from the prehairpin intermediate to the postfusion state. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_28947.map.gz | 5.6 MB | EMDB map data format | |
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Header (meta data) | emd-28947-v30.xml emd-28947.xml | 14.6 KB 14.6 KB | Display Display | EMDB header |
Images | emd_28947.png | 55.7 KB | ||
Filedesc metadata | emd-28947.cif.gz | 5.4 KB | ||
Others | emd_28947_half_map_1.map.gz emd_28947_half_map_2.map.gz | 49.7 MB 49.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-28947 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-28947 | HTTPS FTP |
-Validation report
Summary document | emd_28947_validation.pdf.gz | 646.7 KB | Display | EMDB validaton report |
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Full document | emd_28947_full_validation.pdf.gz | 646.3 KB | Display | |
Data in XML | emd_28947_validation.xml.gz | 12.2 KB | Display | |
Data in CIF | emd_28947_validation.cif.gz | 14.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-28947 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-28947 | HTTPS FTP |
-Related structure data
Related structure data | 8fa1MC 7tikC 8fa2C 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_28947.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.804 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_28947_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_28947_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : SARS-CoV-2 HR1HR2 complex
Entire | Name: SARS-CoV-2 HR1HR2 complex |
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Components |
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-Supramolecule #1: SARS-CoV-2 HR1HR2 complex
Supramolecule | Name: SARS-CoV-2 HR1HR2 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 40 KDa |
-Macromolecule #1: Ferritin, Dps family protein and Spike protein S2' chimera
Macromolecule | Name: Ferritin, Dps family protein and Spike protein S2' chimera 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: 28.774133 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MSHHHHHHGS QTLLRNFGNV YDNPVLLDRS VTAPVTEGFN VVLASFQALY LQYQKHHFVV EGSEFYSLHE FFNESYNQVQ DHIHEIGER LDGLGGVPVA TFSKLAELTC FEQESEGVYS SRQMVENDLA AEQAIIGVIR RQAAQAESLG DRGTRYLYEK I LLKTEERA ...String: MSHHHHHHGS QTLLRNFGNV YDNPVLLDRS VTAPVTEGFN VVLASFQALY LQYQKHHFVV EGSEFYSLHE FFNESYNQVQ DHIHEIGER LDGLGGVPVA TFSKLAELTC FEQESEGVYS SRQMVENDLA AEQAIIGVIR RQAAQAESLG DRGTRYLYEK I LLKTEERA YHLSHFLAKD SLTLGFAYEN QKLIANQFNS AIGKIQDSLS STASALGKLQ DVVNQNAQAL NTLVKQLSSK FG AISSVLN DILSRLDKVE UniProtKB: Ferritin, Dps family protein, Surface glycoprotein |
-Macromolecule #2: Spike protein S2' HR2
Macromolecule | Name: Spike protein S2' HR2 / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 4.935439 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: KNHTSPDVDL GDISGINASV VNIQKEIDRL NEVAKNLNES LIDLQ UniProtKB: Spike glycoprotein |
-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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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 55.0 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: 2.0 µm / Nominal defocus min: 0.3 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: NONE |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.51 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 883152 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |