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- EMDB-27513: Cryo-EM structure of SARS-CoV-2 Gamma (P.1) spike protein in comp... -
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Open data
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Basic information
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Title | Cryo-EM structure of SARS-CoV-2 Gamma (P.1) spike protein in complex with Fab 4A8 | |||||||||
![]() | structure of SARS-CoV-2 Gamma (P.1) spike protein in complex with Fab 4A8 | |||||||||
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Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.59 Å | |||||||||
![]() | Zhu X / Mannar D / Saville JW / Srivastava SS / Berezuk AM / Zhou S / Tuttle KS / Subramaniam S | |||||||||
Funding support | ![]()
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![]() | ![]() Title: SARS-CoV-2 variants of concern: spike protein mutational analysis and epitope for broad neutralization. Authors: Dhiraj Mannar / James W Saville / Zehua Sun / Xing Zhu / Michelle M Marti / Shanti S Srivastava / Alison M Berezuk / Steven Zhou / Katharine S Tuttle / Michele D Sobolewski / Andrew Kim / ...Authors: Dhiraj Mannar / James W Saville / Zehua Sun / Xing Zhu / Michelle M Marti / Shanti S Srivastava / Alison M Berezuk / Steven Zhou / Katharine S Tuttle / Michele D Sobolewski / Andrew Kim / Benjamin R Treat / Priscila Mayrelle Da Silva Castanha / Jana L Jacobs / Simon M Barratt-Boyes / John W Mellors / Dimiter S Dimitrov / Wei Li / Sriram Subramaniam / ![]() ![]() Abstract: Mutations in the spike glycoproteins of SARS-CoV-2 variants of concern have independently been shown to enhance aspects of spike protein fitness. Here, we describe an antibody fragment (V ab6) that ...Mutations in the spike glycoproteins of SARS-CoV-2 variants of concern have independently been shown to enhance aspects of spike protein fitness. Here, we describe an antibody fragment (V ab6) that neutralizes all major variants including the recently emerged BA.1 and BA.2 Omicron subvariants, with a unique mode of binding revealed by cryo-EM studies. Further, we provide a comparative analysis of the mutational effects within previously emerged variant spikes and identify the structural role of mutations within the NTD and RBD in evading antibody neutralization. Our analysis shows that the highly mutated Gamma N-terminal domain exhibits considerable structural rearrangements, partially explaining its decreased neutralization by convalescent sera. Our results provide mechanistic insights into the structural, functional, and antigenic consequences of SARS-CoV-2 spike mutations and highlight a spike protein vulnerability that may be exploited to achieve broad protection against circulating variants. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 123 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 18.3 KB 18.3 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 13.8 KB | Display | ![]() |
Images | ![]() | 66 KB | ||
Others | ![]() ![]() | 226.3 MB 226.3 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8dliC ![]() 8dljC ![]() 8dlkC ![]() 8dllC ![]() 8dlmC ![]() 8dlnC ![]() 8dloC ![]() 8dlpC ![]() 8dlqC ![]() 8dlrC ![]() 8dlsC ![]() 8dltC ![]() 8dluC ![]() 8dlvC ![]() 8dlwC ![]() 8dlxC ![]() 8dlyC ![]() 8dlzC ![]() 8dm0C C: citing same article ( |
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Links
EMDB pages | ![]() ![]() |
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Map
File | ![]() | ||||||||||||||||||||
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Annotation | structure of SARS-CoV-2 Gamma (P.1) spike protein in complex with Fab 4A8 | ||||||||||||||||||||
Voxel size | X=Y=Z: 1 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: Half Map 1
File | emd_27513_half_map_1.map | ||||||||||||
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Annotation | Half Map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half Map 2
File | emd_27513_half_map_2.map | ||||||||||||
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Annotation | Half Map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : SARS-CoV-2 Gamma (P.1) spike protein in complex with Fab 4A8
Entire | Name: SARS-CoV-2 Gamma (P.1) spike protein in complex with Fab 4A8 |
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Components |
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-Supramolecule #1: SARS-CoV-2 Gamma (P.1) spike protein in complex with Fab 4A8
Supramolecule | Name: SARS-CoV-2 Gamma (P.1) spike protein in complex with Fab 4A8 type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() ![]() |
-Supramolecule #2: SARS-CoV-2 Gamma (P.1) spike protein
Supramolecule | Name: SARS-CoV-2 Gamma (P.1) spike protein / type: complex / Chimera: Yes / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() |
-Supramolecule #3: Fab 4A8
Supramolecule | Name: Fab 4A8 / type: complex / Chimera: Yes / ID: 3 / Parent: 1 / Macromolecule list: #2-#3 |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() |
-Macromolecule #1: SARS-CoV-2 Gamma (P.1) spike protein
Macromolecule | Name: SARS-CoV-2 Gamma (P.1) spike protein / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Sequence | String: MFVFLVLLPL VSSQCVNFTN RTQLPSAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHAIHV SGTNGTKRFD NPVLPFNDGV YFASTEKSNI IRGWIFGTTL DSKTQSLLIV NNATNVVIKV CEFQFCNYPF LGVYYHKNNK SWMESEFRVY SSANNCTFEY ...String: MFVFLVLLPL VSSQCVNFTN RTQLPSAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHAIHV SGTNGTKRFD NPVLPFNDGV YFASTEKSNI IRGWIFGTTL DSKTQSLLIV NNATNVVIKV CEFQFCNYPF LGVYYHKNNK SWMESEFRVY SSANNCTFEY VSQPFLMDLE GKQGNFKNLS EFVFKNIDGY FKIYSKHTPI NLVRDLPQGF SALEPLVDLP IGINITRFQT LLALHRSYLT PGDSSSGWTA GAAAYYVGYL QPRTFLLKYN ENGTITDAVD CALDPLSETK CTLKSFTVEK GIYQTSNFRV QPTESIVRFP NITNLCPFGE VFNATRFASV YAWNRKRISN CVADYSVLYN SASFSTFKCY GVSPTKLNDL CFTNVYADSF VIRGDEVRQI APGQTGTIAD YNYKLPDDFT GCVIAWNSNN LDSKVGGNYN YLYRLFRKSN LKPFERDIST EIYQAGSTPC NGVKGFNCYF PLQSYGFQPT YGVGYQPYRV VVLSFELLHA PATVCGPKKS TNLVKNKCVN FNFNGLTGTG VLTESNKKFL PFQQFGRDIA DTTDAVRDPQ TLEILDITPC SFGGVSVITP GTNTSNQVAV LYQGVNCTEV PVAIHADQLT PTWRVYSTGS NVFQTRAGCL IGAEYVNNSY ECDIPIGAGI CASYQTQTNS PGSASSVASQ SIIAYTMSLG AENSVAYSNN SIAIPTNFTI SVTTEILPVS MTKTSVDCTM YICGDSTECS NLLLQYGSFC TQLNRALTGI AVEQDKNTQE VFAQVKQIYK TPPIKDFGGF NFSQILPDPS KPSKRSPIED LLFNKVTLAD AGFIKQYGDC LGDIAARDLI CAQKFNGLTV LPPLLTDEMI AQYTSALLAG TITSGWTFGA GPALQIPFPM QMAYRFNGIG VTQNVLYENQ KLIANQFNSA IGKIQDSLSS TPSALGKLQD VVNQNAQALN TLVKQLSSNF GAISSVLNDI LSRLDPPEAE VQIDRLITGR LQSLQTYVTQ QLIRAAEIRA SANLAAIKMS ECVLGQSKRV DFCGKGYHLM SFPQSAPHGV VFLHVTYVPA QEKNFTTAPA ICHDGKAHFP REGVFVSNGT HWFVTQRNFY EPQIITTDNT FVSGNCDVVI GIVNNTVYDP LQPELDSFKE ELDKYFKNHT SPDVDLGDIS GINASFVNIQ KEIDRLNEVA KNLNESLIDL QELGKYEQGS GYIPEAPRDG QAYVRKDGEW VLLSTFLGRS LEVLFQGPGH HHHHHHHSAW SHPQFEKGGG SGGGGSGGSA WSHPQFEK |
-Macromolecule #2: Fab 4A8 heavy chain
Macromolecule | Name: Fab 4A8 heavy chain / type: protein_or_peptide / ID: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Sequence | String: MDWTWRVFCL LAVAPGAHSE VQLVESGAEV KKPGASVKVS CKVSGYTLTE LSMHWVRQAP GKGLEWMGGF DPEDGETMYA QKFQGRVTMT EDTSTDTAYM ELSSLRSEDT AVYYCATSTA VAGTPDLFDY YYGMDVWGQG TTVTVSSAST KGPSVFPLAP SSKSTSGGTA ...String: MDWTWRVFCL LAVAPGAHSE VQLVESGAEV KKPGASVKVS CKVSGYTLTE LSMHWVRQAP GKGLEWMGGF DPEDGETMYA QKFQGRVTMT EDTSTDTAYM ELSSLRSEDT AVYYCATSTA VAGTPDLFDY YYGMDVWGQG TTVTVSSAST KGPSVFPLAP SSKSTSGGTA ALGCLVKDYF PEPVTVSWNS GALTSGVHTF PAVLQSSGLY SLSSVVTVPS SSLGTQTYIC NVNHKPSNTK VDKKVEPKSC GSHHHHHH |
-Macromolecule #3: Fab 4A8 light chain
Macromolecule | Name: Fab 4A8 light chain / type: protein_or_peptide / ID: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Sequence | String: MVLQTQVFIS LLLWISGAYG EIVMTQSPLS SPVTLGQPAS ISCRSSQSLV HSDGNTYLSW LQQRPGQPPR LLIYKISNRF SGVPDRFSGS GAGTDFTLKI SRVEAEDVGV YYCTQATQFP YTFGQGTKVD IKGQPKANPT VTLFPPSSEE LQANKATLVC LISDFYPGAV ...String: MVLQTQVFIS LLLWISGAYG EIVMTQSPLS SPVTLGQPAS ISCRSSQSLV HSDGNTYLSW LQQRPGQPPR LLIYKISNRF SGVPDRFSGS GAGTDFTLKI SRVEAEDVGV YYCTQATQFP YTFGQGTKVD IKGQPKANPT VTLFPPSSEE LQANKATLVC LISDFYPGAV TVAWKADGSP VKAGVETTKP SKQSNNKYAA SSYLSLTPEQ WKSHRSYSCQ VTHEGSTVEK TVAPTECS |
-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 | TFS KRIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.0 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |