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Yorodumi- EMDB-43097: Simulation-driven design of prefusion stabilized SARS-CoV-2 spike... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-43097 | |||||||||
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Title | Simulation-driven design of prefusion stabilized SARS-CoV-2 spike S2 antigen | |||||||||
Map data | Final refined volume sharpened (DeepEMhance sharpened) | |||||||||
Sample |
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Keywords | SARS-CoV-2 / spike protein / viral fusion / viral glycoprotein / VIRAL PROTEIN | |||||||||
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 / 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 | Severe acute respiratory syndrome coronavirus 2 | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.8 Å | |||||||||
Authors | Zhou L / McLellan JS | |||||||||
Funding support | 1 items
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Citation | Journal: Nat Commun / Year: 2024 Title: Simulation-driven design of stabilized SARS-CoV-2 spike S2 immunogens. Authors: Xandra Nuqui / Lorenzo Casalino / Ling Zhou / Mohamed Shehata / Albert Wang / Alexandra L Tse / Anupam A Ojha / Fiona L Kearns / Mia A Rosenfeld / Emily Happy Miller / Cory M Acreman / Surl- ...Authors: Xandra Nuqui / Lorenzo Casalino / Ling Zhou / Mohamed Shehata / Albert Wang / Alexandra L Tse / Anupam A Ojha / Fiona L Kearns / Mia A Rosenfeld / Emily Happy Miller / Cory M Acreman / Surl-Hee Ahn / Kartik Chandran / Jason S McLellan / Rommie E Amaro / Abstract: The full-length prefusion-stabilized SARS-CoV-2 spike (S) is the principal antigen of COVID-19 vaccines. Vaccine efficacy has been impacted by emerging variants of concern that accumulate most of the ...The full-length prefusion-stabilized SARS-CoV-2 spike (S) is the principal antigen of COVID-19 vaccines. Vaccine efficacy has been impacted by emerging variants of concern that accumulate most of the sequence modifications in the immunodominant S1 subunit. S2, in contrast, is the most evolutionarily conserved region of the spike and can elicit broadly neutralizing and protective antibodies. Yet, S2's usage as an alternative vaccine strategy is hampered by its general instability. Here, we use a simulation-driven approach to design S2-only immunogens stabilized in a closed prefusion conformation. Molecular simulations provide a mechanistic characterization of the S2 trimer's opening, informing the design of tryptophan substitutions that impart kinetic and thermodynamic stabilization. Structural characterization via cryo-EM shows the molecular basis of S2 stabilization in the closed prefusion conformation. Informed by molecular simulations and corroborated by experiments, we report an engineered S2 immunogen that exhibits increased protein expression, superior thermostability, and preserved immunogenicity against sarbecoviruses. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_43097.map.gz | 180.8 MB | EMDB map data format | |
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Header (meta data) | emd-43097-v30.xml emd-43097.xml | 16.4 KB 16.4 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_43097_fsc.xml | 12.6 KB | Display | FSC data file |
Images | emd_43097.png | 42.8 KB | ||
Filedesc metadata | emd-43097.cif.gz | 5.7 KB | ||
Others | emd_43097_additional_1.map.gz emd_43097_half_map_1.map.gz emd_43097_half_map_2.map.gz | 203.8 MB 200.3 MB 200.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-43097 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-43097 | HTTPS FTP |
-Validation report
Summary document | emd_43097_validation.pdf.gz | 806 KB | Display | EMDB validaton report |
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Full document | emd_43097_full_validation.pdf.gz | 805.5 KB | Display | |
Data in XML | emd_43097_validation.xml.gz | 21.6 KB | Display | |
Data in CIF | emd_43097_validation.cif.gz | 28.1 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-43097 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-43097 | HTTPS FTP |
-Related structure data
Related structure data | 8vaoMC 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_43097.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | Final refined volume sharpened (DeepEMhance sharpened) | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.94 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: Final refined volume sharpened (not DeepEMhance sharpened)
File | emd_43097_additional_1.map | ||||||||||||
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Annotation | Final refined volume sharpened (not DeepEMhance sharpened) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map B
File | emd_43097_half_map_1.map | ||||||||||||
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Annotation | Half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map A
File | emd_43097_half_map_2.map | ||||||||||||
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Annotation | Half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : SARS-CoV-2 spike S2 trimer
Entire | Name: SARS-CoV-2 spike S2 trimer |
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Components |
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-Supramolecule #1: SARS-CoV-2 spike S2 trimer
Supramolecule | Name: SARS-CoV-2 spike S2 trimer / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
-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: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 56.323484 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MSLGAENCVA YSNNSIAIPT NFTISVTTEI LPVSMTKTSV DCTMYICGDS TECSNLLLQY GSFCTQLNRA LTGIAVEQDK NTQEVFAQV KQIYCTPPIK DFGGFNFSQI LPDPSKPSKR SPIEDLLFNK VTLADAGFIK QYGDCLGDIA ARDLICAQKF N GLTVLPPL ...String: MSLGAENCVA YSNNSIAIPT NFTISVTTEI LPVSMTKTSV DCTMYICGDS TECSNLLLQY GSFCTQLNRA LTGIAVEQDK NTQEVFAQV KQIYCTPPIK DFGGFNFSQI LPDPSKPSKR SPIEDLLFNK VTLADAGFIK QYGDCLGDIA ARDLICAQKF N GLTVLPPL LTDEMIAQYT SALLAGTITS GWTFGAGPAL QIPFPMQMAY RFNGIGVTQN VLYENQKLIA NQFNSAIGKI QD SLSSTPS ALGKLQDVVN QNAEALNTLV KQLSSNFGAI SSVLNDILSR LDPPEAEWQI DRLIWGRLQS LQTYVTQQLI RAA EIRASA NLAATKMSEC VLGQSKRVDF CGKGYHLMSF PQSAPHGVVF LHVTYVPAQE KNFTTAPAIC HDGKAHFPRE GVFV SNGTH WFVTQRNFYE PQIITTDNTF VSGNCDVVIG IVNNTVYDPL QPELDSFKEE LDKYFKNHTS PDVDLGDISG INASV VNIQ KEIDRLNEVA KNLNESLIDL QELGKYEQ UniProtKB: Spike glycoprotein |
-Macromolecule #2: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 2 / Number of copies: 9 / 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
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | TFS GLACIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 200 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: 1.5 µm |