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Yorodumi- EMDB-41725: Structural and biochemical rationale for Beta variant protein boo... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-41725 | |||||||||
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Title | Structural and biochemical rationale for Beta variant protein booster vaccine broad cross-neutralization of SARS-CoV-2 | |||||||||
Map data | Ancestral_SARS-CoV-2_SPIKE_trimer | |||||||||
Sample |
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Keywords | Spike / trimer / surface / 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 / host cell endoplasmic reticulum-Golgi intermediate compartment membrane ...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 / membrane / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Severe acute respiratory syndrome coronavirus 2 | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.85 Å | |||||||||
Authors | Bruch EM / Rak A | |||||||||
Funding support | 1 items
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Citation | Journal: Sci Rep / Year: 2024 Title: Structural and biochemical rationale for Beta variant protein booster vaccine broad cross-neutralization of SARS-CoV-2. Authors: Eduardo M Bruch / Shaolong Zhu / Lisa Szymkowicz / Taylor Blake / Tara Kiss / D Andrew James / Alexey Rak / Kartik Narayan / Matthew T Balmer / Roman M Chicz / Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, uses a surface expressed trimeric spike glycoprotein for cell entry. This trimer is the primary ...Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, uses a surface expressed trimeric spike glycoprotein for cell entry. This trimer is the primary target for neutralizing antibodies making it a key candidate for vaccine development. During the global pandemic circulating variants of concern (VOC) caused several waves of infection, severe disease, and death. The reduced efficacy of the ancestral trimer-based vaccines against emerging VOC led to the need for booster vaccines. Here we present a detailed characterization of the Sanofi Beta trimer, utilizing cryo-EM for structural elucidation. We investigate the conformational dynamics and stabilizing features using orthogonal SPR, SEC, nanoDSF, and HDX-MS techniques to better understand how this antigen elicits superior broad neutralizing antibodies as a variant booster vaccine. This structural analysis confirms the Beta trimer preference for canonical quaternary structure with two RBD in the up position and the reversible equilibrium between the canonical spike and open trimer conformations. Moreover, this report provides a better understanding of structural differences between spike antigens contributing to differential vaccine efficacy. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_41725.map.gz | 59.6 MB | EMDB map data format | |
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Header (meta data) | emd-41725-v30.xml emd-41725.xml | 15 KB 15 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_41725_fsc.xml | 8.4 KB | Display | FSC data file |
Images | emd_41725.png | 89.6 KB | ||
Filedesc metadata | emd-41725.cif.gz | 6 KB | ||
Others | emd_41725_half_map_1.map.gz emd_41725_half_map_2.map.gz | 59.3 MB 59.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-41725 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-41725 | HTTPS FTP |
-Related structure data
Related structure data | 8tylMC 8tyoC 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_41725.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | Ancestral_SARS-CoV-2_SPIKE_trimer | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.16 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: Ancestral SARS-CoV-2 SPIKE trimer halfB
File | emd_41725_half_map_1.map | ||||||||||||
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Annotation | Ancestral_SARS-CoV-2_SPIKE_trimer_halfB | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Ancestral SARS-CoV-2 SPIKE trimer halfA
File | emd_41725_half_map_2.map | ||||||||||||
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Annotation | Ancestral_SARS-CoV-2_SPIKE_trimer_halfA | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : ancestral SARS-CoV-2 Spike trimer antigen
Entire | Name: ancestral SARS-CoV-2 Spike trimer antigen |
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Components |
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-Supramolecule #1: ancestral SARS-CoV-2 Spike trimer antigen
Supramolecule | Name: ancestral SARS-CoV-2 Spike trimer antigen / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 411.83064 KDa |
-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: 137.840781 KDa |
Recombinant expression | Organism: unidentified baculovirus |
Sequence | String: MPLYKLLNVL WLVAVSNAQC VNLTTRTQLP PAYTNSFTRG VYYPDKVFRS SVLHSTQDLF LPFFSNVTWF HAIHVSGTNG TKRFDNPVL PFNDGVYFAS TEKSNIIRGW IFGTTLDSKT QSLLIVNNAT NVVIKVCEFQ FCNDPFLGVY YHKNNKSWME S EFRVYSSA ...String: MPLYKLLNVL WLVAVSNAQC VNLTTRTQLP PAYTNSFTRG VYYPDKVFRS SVLHSTQDLF LPFFSNVTWF HAIHVSGTNG TKRFDNPVL PFNDGVYFAS TEKSNIIRGW IFGTTLDSKT QSLLIVNNAT NVVIKVCEFQ FCNDPFLGVY YHKNNKSWME S EFRVYSSA NNCTFEYVSQ PFLMDLEGKQ GNFKNLREFV FKNIDGYFKI YSKHTPINLV RDLPQGFSAL EPLVDLPIGI NI TRFQTLL ALHRSYLTPG DSSSGWTAGA AAYYVGYLQP RTFLLKYNEN GTITDAVDCA LDPLSETKCT LKSFTVEKGI YQT SNFRVQ PTESIVRFPN ITNLCPFGEV FNATRFASVY AWNRKRISNC VADYSVLYNS ASFSTFKCYG VSPTKLNDLC FTNV YADSF VIRGDEVRQI APGQTGKIAD YNYKLPDDFT GCVIAWNSNN LDSKVGGNYN YLYRLFRKSN LKPFERDIST EIYQA GSTP CNGVEGFNCY FPLQSYGFQP TNGVGYQPYR VVVLSFELLH APATVCGPKK STNLVKNKCV NFNFNGLTGT GVLTES NKK FLPFQQFGRD IADTTDAVRD PQTLEILDIT PCSFGGVSVI TPGTNTSNEV AVLYQDVNCT EVPVAIHADQ LTPTWRV YS TGSNVFQTRA GCLIGAEHVN NSYECDIPIG AGICASYQTQ TNSPGSASSV ASQSIIAYTM SLGAENSVAY SNNSIAIP T NFTISVTTEI LPVSMTKTSV DCTMYICGDS TECSNLLLQY GSFCTQLNRA LTGIAVEQDK NTQEVFAQVK QIYKTPPIK DFGGFNFSQI LPDPSKPSKR SFIEDLLFNK VTLADAGFIK QYGDCLGDIA ARDLICAQKF NGLTVLPPLL TDEMIAQYTS ALLAGTITS GWTFGAGAAL QIPFAMQMAY RFNGIGVTQN VLYENQKLIA NQFNSAIGKI QDSLSSTASA LGKLQDVVNQ N AQALNTLV KQLSSNFGAI SSVLNDILSR LDPPEAEVQI DRLITGRLQS LQTYVTQQLI RAAEIRASAN LAATKMSECV LG QSKRVDF CGKGYHLMSF PQSAPHGVVF LHVTYVPAQE KNFTTAPAIC HDGKAHFPRE GVFVSNGTHW FVTQRNFYEP QII TTDNTF VSGNCDVVIG IVNNTVYDPL QPELDSFKEE LDKYFKNHTS PDVDLGDISG INASVVNIQK EIDRLNEVAK NLNE SLIDL QELGKYEQYI KGYIPEAPRD GQAYVRKDGE WVFLSTFL 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: 35 / 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 | 3 mg/mL |
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Buffer | pH: 7.5 |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | TFS GLACIOS |
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Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: OTHER / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm |
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 62.0 e/Å2 |