+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-29910 | |||||||||
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Title | SARS-CoV-2 Spike H655Y variant, One RBD Open | |||||||||
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 | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.1 Å | |||||||||
Authors | Egri SB / Shen K / Luban J | |||||||||
Funding support | United States, 1 items
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Citation | Journal: bioRxiv / Year: 2023 Title: S:D614G and S:H655Y are gateway mutations that act epistatically to promote SARS-CoV-2 variant fitness. Authors: Leonid Yurkovetskiy / Shawn Egri / Chaitanya Kurhade / Marco A Diaz-Salinas / Javier A Jaimes / Thomas Nyalile / Xuping Xie / Manish C Choudhary / Ann Dauphin / Jonathan Z Li / James B Munro ...Authors: Leonid Yurkovetskiy / Shawn Egri / Chaitanya Kurhade / Marco A Diaz-Salinas / Javier A Jaimes / Thomas Nyalile / Xuping Xie / Manish C Choudhary / Ann Dauphin / Jonathan Z Li / James B Munro / Pei-Yong Shi / Kuang Shen / Jeremy Luban / Abstract: SARS-CoV-2 variants bearing complex combinations of mutations that confer increased transmissibility, COVID-19 severity, and immune escape, were first detected after S:D614G had gone to fixation, and ...SARS-CoV-2 variants bearing complex combinations of mutations that confer increased transmissibility, COVID-19 severity, and immune escape, were first detected after S:D614G had gone to fixation, and likely originated during persistent infection of immunocompromised hosts. To test the hypothesis that S:D614G facilitated emergence of such variants, S:D614G was reverted to the ancestral sequence in the context of sequential Spike sequences from an immunocompromised individual, and within each of the major SARS-CoV-2 variants of concern. In all cases, infectivity of the S:D614G revertants was severely compromised. The infectivity of atypical SARS-CoV-2 lineages that propagated in the absence of S:D614G was found to be dependent upon either S:Q613H or S:H655Y. Notably, Gamma and Omicron variants possess both S:D614G and S:H655Y, each of which contributed to infectivity of these variants. Among sarbecoviruses, S:Q613H, S:D614G, and S:H655Y are only detected in SARS-CoV-2, which is also distinguished by a polybasic S1/S2 cleavage site. Genetic and biochemical experiments here showed that S:Q613H, S:D614G, and S:H655Y each stabilize Spike on virions, and that they are dispensable in the absence of S1/S2 cleavage, consistent with selection of these mutations by the S1/S2 cleavage site. CryoEM revealed that either S:D614G or S:H655Y shift the Spike receptor binding domain (RBD) towards the open conformation required for ACE2-binding and therefore on pathway for infection. Consistent with this, an smFRET reporter for RBD conformation showed that both S:D614G and S:H655Y spontaneously adopt the conformation that ACE2 induces in the parental Spike. Data from these orthogonal experiments demonstrate that S:D614G and S:H655Y are convergent adaptations to the polybasic S1/S2 cleavage site which stabilize S1 on the virion in the open RBD conformation and act epistatically to promote the fitness of variants bearing complex combinations of clinically significant mutations. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_29910.map.gz | 228.2 MB | EMDB map data format | |
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Header (meta data) | emd-29910-v30.xml emd-29910.xml | 14.5 KB 14.5 KB | Display Display | EMDB header |
Images | emd_29910.png | 88.4 KB | ||
Others | emd_29910_half_map_1.map.gz emd_29910_half_map_2.map.gz | 194.1 MB 194.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-29910 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-29910 | HTTPS FTP |
-Validation report
Summary document | emd_29910_validation.pdf.gz | 784.7 KB | Display | EMDB validaton report |
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Full document | emd_29910_full_validation.pdf.gz | 784.3 KB | Display | |
Data in XML | emd_29910_validation.xml.gz | 15.4 KB | Display | |
Data in CIF | emd_29910_validation.cif.gz | 18.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29910 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29910 | HTTPS FTP |
-Related structure data
Related structure data | 8gb0MC 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_29910.map.gz / Format: CCP4 / Size: 244.1 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: 1.05 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_29910_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_29910_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : SARS-CoV-2 Spike H655Y variant, One RBD Open
Entire | Name: SARS-CoV-2 Spike H655Y variant, One RBD Open |
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Components |
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-Supramolecule #1: SARS-CoV-2 Spike H655Y variant, One RBD Open
Supramolecule | Name: SARS-CoV-2 Spike H655Y variant, One RBD Open / type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
-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: 142.500219 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MFMPSSFSYS SWATCWLLCC LIILAKATMF VFLVLLPLVS SQCVNLTTRT QLPPAYTNSF TRGVYYPDKV FRSSVLHSTQ DLFLPFFSN VTWFHAIHVS GTNGTKRFDN PVLPFNDGVY FASTEKSNII RGWIFGTTLD SKTQSLLIVN NATNVVIKVC E FQFCNDPF ...String: MFMPSSFSYS SWATCWLLCC LIILAKATMF VFLVLLPLVS SQCVNLTTRT QLPPAYTNSF TRGVYYPDKV FRSSVLHSTQ DLFLPFFSN VTWFHAIHVS GTNGTKRFDN PVLPFNDGVY FASTEKSNII RGWIFGTTLD SKTQSLLIVN NATNVVIKVC E FQFCNDPF LGVYYHKNNK SWMESEFRVY SSANNCTFEY VSQPFLMDLE GKQGNFKNLR EFVFKNIDGY FKIYSKHTPI NL VRDLPQG FSALEPLVDL PIGINITRFQ TLLALHRSYL TPGDSSSGWT AGAAAYYVGY LQPRTFLLKY NENGTITDAV DCA LDPLSE TKCTLKSFTV EKGIYQTSNF RVQPTESIVR FPNITNLCPF GEVFNATRFA SVYAWNRKRI SNCVADYSVL YNSA SFSTF KCYGVSPTKL NDLCFTNVYA DSFVIRGDEV RQIAPGQTGK IADYNYKLPD DFTGCVIAWN SNNLDSKVGG NYNYL YRLF RKSNLKPFER DISTEIYQAG STPCNGVEGF NCYFPLQSYG FQPTNGVGYQ PYRVVVLSFE LLHAPATVCG PKKSTN LVK NKCVNFNFNG LTGTGVLTES NKKFLPFQQF GRDIADTTDA VRDPQTLEIL DITPCSFGGV SVITPGTNTS NEVAVLY QD VNCTEVPVAI HADQLTPTWR VYSTGSNVFQ TRAGCLIGAE YVNNSYECDI PIGAGICASY QTQTNSPASV ASQSIIAY T MSLGAENSVA YSNNSIAIPT NFTISVTTEI LPVSMTKTSV DCTMYICGDS TECSNLLLQY GSFCTQLNRA LTGIAVEQD KNTQEVFAQV KQIYKTPPIK DFGGFNFSQI LPDPSKPSKR SFIEDLLFNK VTLADAGFIK QYGDCLGDIA ARDLICAQKF NGLTVLPPL LTDEMIAQYT SALLAGTITS GWTFGAGAAL QIPFAMQMAY RFNGIGVTQN VLYENQKLIA NQFNSAIGKI Q DSLSSTAS ALGKLQDVVN QNAQALNTLV KQLSSNFGAI SSVLNDILSR LDPPEAEVQI DRLITGRLQS LQTYVTQQLI RA AEIRASA NLAATKMSEC VLGQSKRVDF CGKGYHLMSF PQSAPHGVVF LHVTYVPAQE KNFTTAPAIC HDGKAHFPRE GVF VSNGTH WFVTQRNFYE PQIITTDNTF VSGNCDVVIG IVNNTVYDPL QPELDSFKEE LDKYFKNHTS PDVDLGDISG INAS VVNIQ KEIDRLNEVA KNLNESLIDL QELGKYEQYI KWPSGRLVPR GSPGSGYIPE APRDGQAYVR KDGEWVLLST FLGHH HHHH |
-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 K2 SUMMIT (4k x 4k) / Average electron dose: 37.2 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: 1.8 µm / Nominal defocus min: 0.6 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: EMDB MAP EMDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 420953 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |