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Yorodumi- EMDB-40814: Local refinement of SARS-CoV-2 (HP-GSAS-Mut7) spike NTD in comple... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-40814 | |||||||||
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Title | Local refinement of SARS-CoV-2 (HP-GSAS-Mut7) spike NTD in complex with TXG-0078 Fab | |||||||||
Map data | EM map | |||||||||
Sample |
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Keywords | SARS-CoV-2 / spike / COVID / monoclonal antibody / complex / NTD / 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 / 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 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.88 Å | |||||||||
Authors | Bangaru B / Ward A | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Cell Rep / Year: 2024 Title: Deep repertoire mining uncovers ultra-broad coronavirus neutralizing antibodies targeting multiple spike epitopes. Authors: Jonathan Hurtado / Thomas F Rogers / David B Jaffe / Bruce A Adams / Sandhya Bangaru / Elijah Garcia / Tazio Capozzola / Terrence Messmer / Pragati Sharma / Ge Song / Nathan Beutler / ...Authors: Jonathan Hurtado / Thomas F Rogers / David B Jaffe / Bruce A Adams / Sandhya Bangaru / Elijah Garcia / Tazio Capozzola / Terrence Messmer / Pragati Sharma / Ge Song / Nathan Beutler / Wanting He / Katharina Dueker / Rami Musharrafieh / Sarah Burbach / Alina Truong / Michael J T Stubbington / Dennis R Burton / Raiees Andrabi / Andrew B Ward / Wyatt J McDonnell / Bryan Briney / Abstract: The development of vaccines and therapeutics that are broadly effective against known and emergent coronaviruses is an urgent priority. We screened the circulating B cell repertoires of COVID-19 ...The development of vaccines and therapeutics that are broadly effective against known and emergent coronaviruses is an urgent priority. We screened the circulating B cell repertoires of COVID-19 survivors and vaccinees to isolate over 9,000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific monoclonal antibodies (mAbs), providing an expansive view of the SARS-CoV-2-specific Ab repertoire. Among the recovered antibodies was TXG-0078, an N-terminal domain (NTD)-specific neutralizing mAb that recognizes diverse alpha- and beta-coronaviruses. TXG-0078 achieves its exceptional binding breadth while utilizing the same VH1-24 variable gene signature and heavy-chain-dominant binding pattern seen in other NTD-supersite-specific neutralizing Abs with much narrower specificity. We also report CC24.2, a pan-sarbecovirus neutralizing antibody that targets a unique receptor-binding domain (RBD) epitope and shows similar neutralization potency against all tested SARS-CoV-2 variants, including BQ.1.1 and XBB.1.5. A cocktail of TXG-0078 and CC24.2 shows protection in vivo, suggesting their potential use in variant-resistant therapeutic Ab cocktails and as templates for pan-coronavirus vaccine design. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_40814.map.gz | 506.3 MB | EMDB map data format | |
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Header (meta data) | emd-40814-v30.xml emd-40814.xml | 22.1 KB 22.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_40814_fsc.xml | 18.3 KB | Display | FSC data file |
Images | emd_40814.png | 43.4 KB | ||
Masks | emd_40814_msk_1.map | 536.4 MB | Mask map | |
Filedesc metadata | emd-40814.cif.gz | 7.9 KB | ||
Others | emd_40814_half_map_1.map.gz emd_40814_half_map_2.map.gz | 497.7 MB 497.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-40814 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-40814 | HTTPS FTP |
-Validation report
Summary document | emd_40814_validation.pdf.gz | 976.8 KB | Display | EMDB validaton report |
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Full document | emd_40814_full_validation.pdf.gz | 976.3 KB | Display | |
Data in XML | emd_40814_validation.xml.gz | 26.5 KB | Display | |
Data in CIF | emd_40814_validation.cif.gz | 34.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-40814 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-40814 | HTTPS FTP |
-Related structure data
Related structure data | 8swhMC 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_40814.map.gz / Format: CCP4 / Size: 536.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | EM map | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.725 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_40814_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: half map 1
File | emd_40814_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_40814_half_map_2.map | ||||||||||||
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Annotation | Half map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Structure of SARS-CoV-2(HP-GSAS-Mut7) spike in complex with TXG-0...
Entire | Name: Structure of SARS-CoV-2(HP-GSAS-Mut7) spike in complex with TXG-0078 Fab- Local refinement |
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Components |
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-Supramolecule #1: Structure of SARS-CoV-2(HP-GSAS-Mut7) spike in complex with TXG-0...
Supramolecule | Name: Structure of SARS-CoV-2(HP-GSAS-Mut7) spike in complex with TXG-0078 Fab- Local refinement type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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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: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 141.328359 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHAIHV SGTNGTKRFD NPVLPFNDG VYFASTEKSN IIRGWIFGTT LDSKTQSLLI VNNATNVVIK VCEFQFCNDP FLGVYYHKNN KSWMESEFRV Y SSANNCTF ...String: MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHAIHV SGTNGTKRFD NPVLPFNDG VYFASTEKSN IIRGWIFGTT LDSKTQSLLI VNNATNVVIK VCEFQFCNDP FLGVYYHKNN KSWMESEFRV Y SSANNCTF EYVSQPFLMD LEGKQGNFKN LREFVFKNID GYFKIYSKHT PINLVRDLPQ GFSALEPLVD LPIGINITRF QT LLALHRS YLTPGDSSSG WTAGAAAYYV GYLQPRTFLL KYNENGTITD AVDCALDPLS ETKCTLKSFT VEKGIYQTSN FRV QPTESI VRFPNITNLC PFGEVFNATR FASVYAWNRK RISNCVADYS VLYNSASFST FKCYGVSPTK LNDLCFTNVY ADSF VIRGD EVRQIAPGQT GKIADYNYKL PDDFTGCVIA WNSNNLDSKV GGNYNYLYRL FRKSNLKPFE RDISTEIYQA GSTPC NGVE GFNCYFPLQS YGFQPTNGVG YQPYRVVVLS FELLHAPATV CGPKKSTNLV KNKCVNFNFN GLTGTGVLTE SNKKFL PFQ QFGRDIADTT DAVRDPQTLE ILDITPCSFG GVSVITPGTN TSNQVAVLYQ DVNCTEVPVA IHADQLTPTW RVYSTGS NV FQTRAGCLIG AEHVNNSYEC DIPIGAGICA SYQTQTNSPG SASSVASQSI IAYTMSLGAE NSCAYSNNSI AIPTNFTI S VTTEILPVSM TKTSVDCTMY ICGDSTECSN LLLQYGSFCT QLNRALTGIA VEQDKNTQEV FAQVKQIYKT PPIKDFGGF NFSQILPDPS KPSKRSPIED LLFNKVTLAD AGFIKQYGDC LGDIAARDLI CAQKFNGLTV LPPLLTDEMI AQYTSALLAG TICSGWTFG AGPALQIPFP MQMAYRFNGI GVTQNVLYEN QKLIANQFNS AIGKIQDSLS STPSALGKLQ DVVNQNAQAL N TLVKQLSS NFGAISSVLN DILSRLDPPE AEVQIDRLIT GRLQSLQTYV TQQLIRAAEI RASANLAATK MSECVLGQSK RV DFCGKGY HLMSFPQSAP HGVVFLHVTY VPAQEKNFTT APAICHDGKA HFPREGVFVS NGTHWFVTQR NFYEPQIITT DNT FVSGNC DVVIGIVNNT VYDPLQPELD SFKEELDKYF KNHTSPDVDL GDISGINASV VNIQKEIDRL NEVAKNLNES LIDL QELGK YEQGSGYIPE APRDGQAYVR KDGEWVLLST FLGRSLEVLF QGPGSAWSHP QFEKGGGSGG GGSGGSAWSH PQFEK UniProtKB: Spike glycoprotein |
-Macromolecule #2: TXG-0078 Fab Heavy chain
Macromolecule | Name: TXG-0078 Fab Heavy chain / 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: 16.115957 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MDCTWRILFL VAAATGTHAQ VQVIQSGAEV KKPGASVKVS CKVSGYTLTE LSIHWVRQAP GKGLEWMGGF DPEDAETIYA QQFQGRVSM TEDTSTDTAY MELSSLRSED TAVYYCATAF AITTVGTNYY YYYGMDVWGQ GTTVTVSS |
-Macromolecule #3: TXG-0078 Fab Light chain
Macromolecule | Name: TXG-0078 Fab Light chain / 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: 14.484454 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MRLLAQLLGL LMLWVPESSG DIVLTQTPLS SPVTLGQPAS ISCRSSQSLV HSDGNTYLSW LQQRPGQPPR LLIYKISNRF SGVPDRFSG SGAGTDFTLK ISRVEAEDVG LYYCTQATQF PHTFGQGTRL DIK |
-Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 2 / 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 | 1 mg/mL | |||||||||
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Buffer | pH: 7.4 Component:
Details: 1X TBS | |||||||||
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Pretreatment - Type: PLASMA CLEANING / Pretreatment - Time: 10 sec. | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 283 K / Instrument: FEI VITROBOT MARK IV | |||||||||
Details | The spike protein was incubated with a 3-fold molar excess of TXG-0078 Fab for 30 minutes and mixed with 0.04 mM Lauryl maltose neopentyl glycol solution immediately prior to sample deposition. |
-Electron microscopy
Microscope | TFS GLACIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Detector mode: COUNTING / Number grids imaged: 1 / Number real images: 4257 / 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 / Cs: 2.7 mm / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.5 µm / Nominal magnification: 190000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |