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Yorodumi- EMDB-35155: Local CryoEM structure of the SARS-CoV-2 S6P in complex with 7B3 Fab -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-35155 | |||||||||
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Title | Local CryoEM structure of the SARS-CoV-2 S6P in complex with 7B3 Fab | |||||||||
Map data | ||||||||||
Sample |
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Keywords | SARS-Cov-2 / receptor binding domain / RBD / Fab / coronavirus / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
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 / 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 | Homo sapiens (human) / Severe acute respiratory syndrome coronavirus 2 | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||
Authors | Li Z / Yu F / Cao S / ZHao H | |||||||||
Funding support | China, 1 items
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Citation | Journal: Signal Transduct Target Ther / Year: 2023 Title: Broadly neutralizing antibodies derived from the earliest COVID-19 convalescents protect mice from SARS-CoV-2 variants challenge. Authors: Qianyun Liu / Haiyan Zhao / Zhiqiang Li / Zhen Zhang / Rui Huang / Mengxue Gu / Ke Zhuang / Qing Xiong / Xianying Chen / Weiyi Yu / Shengnan Qian / Yuzhen Zhang / Xue Tan / Muyi Zhang / ...Authors: Qianyun Liu / Haiyan Zhao / Zhiqiang Li / Zhen Zhang / Rui Huang / Mengxue Gu / Ke Zhuang / Qing Xiong / Xianying Chen / Weiyi Yu / Shengnan Qian / Yuzhen Zhang / Xue Tan / Muyi Zhang / Feiyang Yu / Ming Guo / Zhixiang Huang / Xin Wang / Wenjie Xiang / Bihao Wu / Fanghua Mei / Kun Cai / Limin Zhou / Li Zhou / Ying Wu / Huan Yan / Sheng Cao / Ke Lan / Yu Chen / Abstract: Coronavirus disease 2019 (COVID-19) was first reported three years ago, when a group of individuals were infected with the original SARS-CoV-2 strain, based on which vaccines were developed. Here, we ...Coronavirus disease 2019 (COVID-19) was first reported three years ago, when a group of individuals were infected with the original SARS-CoV-2 strain, based on which vaccines were developed. Here, we develop six human monoclonal antibodies (mAbs) from two elite convalescents in Wuhan and show that these mAbs recognize diverse epitopes on the receptor binding domain (RBD) and can inhibit the infection of SARS-CoV-2 original strain and variants of concern (VOCs) to varying degrees, including Omicron strains XBB and XBB.1.5. Of these mAbs, the two most broadly and potently neutralizing mAbs (7B3 and 14B1) exhibit prophylactic activity against SARS-CoV-2 WT infection and therapeutic effects against SARS-CoV-2 Delta variant challenge in K18-hACE2 KI mice. Furthermore, post-exposure treatment with 7B3 protects mice from lethal Omicron variants infection. Cryo-EM analysis of the spike trimer complexed with 14B1 or 7B3 reveals that these two mAbs bind partially overlapped epitopes onto the RBD of the spike, and sterically disrupt the binding of human angiotensin-converting enzyme 2 (hACE2) to RBD. Our results suggest that mAbs with broadly neutralizing activity against different SARS-CoV-2 variants are present in COVID-19 convalescents infected by the ancestral SARS-CoV-2 strain, indicating that people can benefit from former infections or vaccines despite the extensive immune escape of SARS-CoV-2. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_35155.map.gz | 203.9 MB | EMDB map data format | |
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Header (meta data) | emd-35155-v30.xml emd-35155.xml | 20.1 KB 20.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_35155_fsc.xml | 12.7 KB | Display | FSC data file |
Images | emd_35155.png | 59.4 KB | ||
Masks | emd_35155_msk_1.map | 216 MB | Mask map | |
Filedesc metadata | emd-35155.cif.gz | 6.9 KB | ||
Others | emd_35155_additional_1.map.gz emd_35155_half_map_1.map.gz emd_35155_half_map_2.map.gz | 204.2 MB 200.2 MB 200.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-35155 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-35155 | HTTPS FTP |
-Validation report
Summary document | emd_35155_validation.pdf.gz | 1017.6 KB | Display | EMDB validaton report |
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Full document | emd_35155_full_validation.pdf.gz | 1017.1 KB | Display | |
Data in XML | emd_35155_validation.xml.gz | 21.5 KB | Display | |
Data in CIF | emd_35155_validation.cif.gz | 27.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35155 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35155 | HTTPS FTP |
-Related structure data
Related structure data | 8i3sMC 8i3uC 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_35155.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.95 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_35155_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: #1
File | emd_35155_additional_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_35155_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_35155_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Spike-Fab complex
Entire | Name: Spike-Fab complex |
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Components |
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-Supramolecule #1: Spike-Fab complex
Supramolecule | Name: Spike-Fab complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Spike glycoprotein
Macromolecule | Name: Spike glycoprotein / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 137.897609 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QCVNLTTRTQ LPPAYTNSFT RGVYYPDKVF RSSVLHSTQD LFLPFFSNVT WFHAIHVSGT NGTKRFDNPV LPFNDGVYFA STEKSNIIR GWIFGTTLDS KTQSLLIVNN ATNVVIKVCE FQFCNDPFLG VYYHKNNKSW MESEFRVYSS ANNCTFEYVS Q PFLMDLEG ...String: QCVNLTTRTQ LPPAYTNSFT RGVYYPDKVF RSSVLHSTQD LFLPFFSNVT WFHAIHVSGT NGTKRFDNPV LPFNDGVYFA STEKSNIIR GWIFGTTLDS KTQSLLIVNN ATNVVIKVCE FQFCNDPFLG VYYHKNNKSW MESEFRVYSS ANNCTFEYVS Q PFLMDLEG KQGNFKNLRE FVFKNIDGYF KIYSKHTPIN LVRDLPQGFS ALEPLVDLPI GINITRFQTL LALHRSYLTP GD SSSGWTA GAAAYYVGYL QPRTFLLKYN ENGTITDAVD CALDPLSETK CTLKSFTVEK GIYQTSNFRV QPTESIVRFP NIT NLCPFG EVFNATRFAS VYAWNRKRIS NCVADYSVLY NSASFSTFKC YGVSPTKLND LCFTNVYADS FVIRGDEVRQ IAPG QTGKI ADYNYKLPDD FTGCVIAWNS NNLDSKVGGN YNYLYRLFRK SNLKPFERDI STEIYQAGST PCNGVEGFNC YFPLQ SYGF QPTNGVGYQP YRVVVLSFEL LHAPATVCGP KKSTNLVKNK CVNFNFNGLT GTGVLTESNK KFLPFQQFGR DIADTT DAV RDPQTLEILD ITPCSFGGVS VITPGTNTSN QVAVLYQDVN CTEVPVAIHA DQLTPTWRVY STGSNVFQTR AGCLIGA EH VNNSYECDIP IGAGICASYQ TQTNSPASVA SQSIIAYTMS LGAENSVAYS NNSIAIPTNF TISVTTEILP VSMTKTSV D CTMYICGDST ECSNLLLQYG SFCTQLNRAL TGIAVEQDKN TQEVFAQVKQ IYKTPPIKDF GGFNFSQILP DPSKPSKRS PIEDLLFNKV TLADAGFIKQ YGDCLGDIAA RDLICAQKFN GLTVLPPLLT DEMIAQYTSA LLAGTITSGW TFGAGPALQI PFPMQMAYR FNGIGVTQNV LYENQKLIAN QFNSAIGKIQ DSLSSTPSAL GKLQDVVNQN AQALNTLVKQ LSSNFGAISS V LNDILSRL DPPEAEVQID RLITGRLQSL QTYVTQQLIR AAEIRASANL AATKMSECVL GQSKRVDFCG KGYHLMSFPQ SA PHGVVFL HVTYVPAQEK NFTTAPAICH DGKAHFPREG VFVSNGTHWF VTQRNFYEPQ IITTDNTFVS GNCDVVIGIV NNT VYDPLQ PELDSFKEEL DKYFKNHTSP DVDLGDISGI NASVVNIQKE IDRLNEVAKN LNESLIDLQE LGKYEQYIKW PSGR LVPRG SPGSGYIPEA PRDGQAYVRK DGEWVLLSTF LGHHHHHH UniProtKB: Spike glycoprotein |
-Macromolecule #2: Heavy chain od Fab 7B3
Macromolecule | Name: Heavy chain od Fab 7B3 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 24.534648 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLVQSGAE MKNFGSSVKV SCKASGGTFS INWVRQAPGL GLEYMGRIIP ALDRAIYTQK FQGRVTITAD KSTSTVYMEL SGLRSEDTA VYYCARSVVG PTPNYFDPWG QGTLVTVSSA STKGPSVFPL APSSKSTSGG TAALGCLVKD YFPEPVTVSW N SGALTSGV ...String: QVQLVQSGAE MKNFGSSVKV SCKASGGTFS INWVRQAPGL GLEYMGRIIP ALDRAIYTQK FQGRVTITAD KSTSTVYMEL SGLRSEDTA VYYCARSVVG PTPNYFDPWG QGTLVTVSSA STKGPSVFPL APSSKSTSGG TAALGCLVKD YFPEPVTVSW N SGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKVEP KSCDKTHHHH HH |
-Macromolecule #3: Light chain of Fab 7B3
Macromolecule | Name: Light chain of Fab 7B3 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.278826 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EIVMTQSPAT LSVSPGERAT LSCRASQSVS SDLAWYQQKR GQAPRLLIYG ASTRATGIPA RFSGSGSGTE FTLTISSLQS EDFAVYYCQ QYNNFIAFGQ GTRLEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ E SVTEQDSK ...String: EIVMTQSPAT LSVSPGERAT LSCRASQSVS SDLAWYQQKR GQAPRLLIYG ASTRATGIPA RFSGSGSGTE FTLTISSLQS EDFAVYYCQ QYNNFIAFGQ GTRLEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ E SVTEQDSK DSTYSLSSTL TLSKADYEKH KVYACEVTHQ GLSSPVTKSF NRGEC |
-Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 1 / 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 | JEOL CRYO ARM 300 |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 40.0 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: 2.5 µm / Nominal defocus min: 0.5 µm |