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- EMDB-43437: Prefusion stabilized structure of the SARS-CoV-2 fusion machinery -
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Open data
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Basic information
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Title | Prefusion stabilized structure of the SARS-CoV-2 fusion machinery | |||||||||
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![]() | Sarbecoviruses / Spike glycoprotein / fusion protein / prefusion-stabilized / Seattle Structural Genomics Center for Infectious Disease / SSGCID / viral protein | |||||||||
Function / homology | ![]() 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 / 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 | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | |||||||||
![]() | Lee J / Veesler D / Seattle Structural Genomics Center for Infectious Disease (SSGCID) | |||||||||
Funding support | ![]()
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![]() | ![]() Title: A broadly generalizable stabilization strategy for sarbecovirus fusion machinery vaccines. Authors: Jimin Lee / Cameron Stewart / Alexandra Schäfer / Elizabeth M Leaf / Young-Jun Park / Daniel Asarnow / John M Powers / Catherine Treichel / Kaitlin R Sprouse / Davide Corti / Ralph Baric / ...Authors: Jimin Lee / Cameron Stewart / Alexandra Schäfer / Elizabeth M Leaf / Young-Jun Park / Daniel Asarnow / John M Powers / Catherine Treichel / Kaitlin R Sprouse / Davide Corti / Ralph Baric / Neil P King / David Veesler / ![]() ![]() Abstract: Evolution of SARS-CoV-2 alters the antigenicity of the immunodominant spike (S) receptor-binding domain and N-terminal domain, undermining the efficacy of vaccines and antibody therapies. To overcome ...Evolution of SARS-CoV-2 alters the antigenicity of the immunodominant spike (S) receptor-binding domain and N-terminal domain, undermining the efficacy of vaccines and antibody therapies. To overcome this challenge, we set out to develop a vaccine focusing antibody responses on the highly conserved but metastable S subunit, which folds as a spring-loaded fusion machinery. We describe a strategy for prefusion-stabilization and high yield recombinant production of SARS-CoV-2 S trimers with native structure and antigenicity. We demonstrate that our design strategy is broadly generalizable to sarbecoviruses, as exemplified with the SARS-CoV-1 (clade 1a) and PRD-0038 (clade 3) S subunits. Immunization of mice with a prefusion-stabilized SARS-CoV-2 S trimer elicits broadly reactive sarbecovirus antibodies and neutralizing antibody titers of comparable magnitude against Wuhan-Hu-1 and the immune evasive XBB.1.5 variant. Vaccinated mice were protected from weight loss and disease upon challenge with XBB.1.5, providing proof-of-principle for fusion machinery sarbecovirus vaccines. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 259.3 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 16.7 KB 16.7 KB | Display Display | ![]() |
Images | ![]() | 68.9 KB | ||
Filedesc metadata | ![]() | 5.9 KB | ||
Others | ![]() ![]() ![]() | 137.3 MB 255.2 MB 255.2 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8vqbMC ![]() 8vq9C ![]() 8vqaC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 0.843 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: #1
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Density Histograms |
-Half map: #2
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Density Histograms |
-Half map: #1
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Density Histograms |
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Sample components
-Entire : Prefusion stabilized structure of the SARS-CoV-2 fusion machinery
Entire | Name: Prefusion stabilized structure of the SARS-CoV-2 fusion machinery |
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Components |
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-Supramolecule #1: Prefusion stabilized structure of the SARS-CoV-2 fusion machinery
Supramolecule | Name: Prefusion stabilized structure of the SARS-CoV-2 fusion machinery type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Spike protein S2
Macromolecule | Name: Spike protein S2 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 68.305328 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MGILPSPGMP ALLSLVSLLS VLLMGCVAET GTSVASQSII AYTMSLGAEN SVACSNNSIA IPTNFTISVT TEILPVSMTK TSVDCTMYI CGDSTECSNL LLQYGSFCTQ LNRALTGIAV EQDKNTQEVF AQVKQIYKTP PIKDFGGFNF SQILPDPSKP S KRSFIEDL ...String: MGILPSPGMP ALLSLVSLLS VLLMGCVAET GTSVASQSII AYTMSLGAEN SVACSNNSIA IPTNFTISVT TEILPVSMTK TSVDCTMYI CGDSTECSNL LLQYGSFCTQ LNRALTGIAV EQDKNTQEVF AQVKQIYKTP PIKDFGGFNF SQILPDPSKP S KRSFIEDL LFNKVTLADA GFIKQYGDCL GDIAARDLIC AQKFNGLTVL PPLLTDEMIA QYTSALLAGT ICSGWTFGAG PA LQIPFPM QMAYRFEGIG VTQNVLYENQ KLIANQFNSA IGKIQDSLSS TPSALGKLQD VVNQNAQALN FLVKQLSSNC GAI SSVLND ILSRLDKPEA EVQIQRLITC RLQSLQTYVT QMLIRAAEYR ASANLAATKM SECVLGQSKR VDFCGKGYHL MSFP QSAPH GVVFLHVTYV PAQEKNFTTA PAICHDGKAH FPREGVFVSN GTHWFVTQRN FYEPQIITTD NTFVSGNCDV VIGIV NNTV YDPLQPELDS FKEELDKYFK NHTSPDVDLG DISGINASVV NIQKEIDRLN EVAKNLNESL IDLQELGKYE QGSGYI PEA PRDGQAYVRK DGEWVLLSTF LGRSLEVLFQ GPGSGGLNDI FEAQKIEWHE GSGHHHHHHH H UniProtKB: Spike glycoprotein |
-Macromolecule #3: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 3 / Number of copies: 6 / 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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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 63.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.27 µm / Nominal defocus min: 0.1 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: NONE |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 319001 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |