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- EMDB-40812: Structure of SARS-CoV-2 (HP-GSAS-Mut7) spike in complex with TXG-... -

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Basic information

Entry
Database: EMDB / ID: EMD-40812
TitleStructure of SARS-CoV-2 (HP-GSAS-Mut7) spike in complex with TXG-0078 Fab -Conformation 1
Map dataSharpened map
Sample
  • Complex: Structure of SARS-CoV-2 (HP-GSAS-Mut7) spike in complex with TXG-0078 Fab -Conformation 1
    • Protein or peptide: SARS-CoV-2 spike (HP-GSAS-Mut7)
KeywordsSARS-CoV-2 / spike / COVID / monoclonal antibody / complex / NTD / VIRAL PROTEIN
Biological speciesSevere acute respiratory syndrome coronavirus 2
Methodsingle particle reconstruction / cryo EM / Resolution: 3.17 Å
AuthorsBangaru S / Ward AB
Funding support United States, 2 items
OrganizationGrant numberCountry
Bill & Melinda Gates FoundationOPP1170236 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)P01 AI144462 United States
CitationJournal: 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
DepositionMay 18, 2023-
Header (metadata) releaseJun 5, 2024-
Map releaseJun 5, 2024-
UpdateJun 26, 2024-
Current statusJun 26, 2024Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_40812.png

Downloads & links

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Map

FileDownload / File: emd_40812.map.gz / Format: CCP4 / Size: 536.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationSharpened map
Projections & slices

Image control

Size
Brightness
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AxesZ (Sec.)Y (Row.)X (Col.)
0.73 Å/pix.
x 520 pix.
= 377. Å		0.73 Å/pix.
x 520 pix.
= 377. Å		0.73 Å/pix.
x 520 pix.
= 377. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.725 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.003
Minimum - Maximum-0.015188151 - 0.027684802
Average (Standard dev.)0.0000016427175 (±0.00065832067)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions520520520
Spacing520520520
CellA=B=C: 377.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_40812_msk_1.map
Projections & Slices
AxesZYX

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Density Histograms

Histogram

Histogram (log scale)

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Half map: Half-map 2

Fileemd_40812_half_map_1.map
AnnotationHalf-map 2
Projections & Slices
AxesZYX

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Histogram

Histogram (log scale)

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Half map: Half-map 1

Fileemd_40812_half_map_2.map
AnnotationHalf-map 1
Projections & Slices
AxesZYX

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Histogram

Histogram (log scale)

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Sample components

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Entire : Structure of SARS-CoV-2 (HP-GSAS-Mut7) spike in complex with TXG-...

EntireName: Structure of SARS-CoV-2 (HP-GSAS-Mut7) spike in complex with TXG-0078 Fab -Conformation 1
Components
  • Complex: Structure of SARS-CoV-2 (HP-GSAS-Mut7) spike in complex with TXG-0078 Fab -Conformation 1
    • Protein or peptide: SARS-CoV-2 spike (HP-GSAS-Mut7)

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Supramolecule #1: Structure of SARS-CoV-2 (HP-GSAS-Mut7) spike in complex with TXG-...

SupramoleculeName: Structure of SARS-CoV-2 (HP-GSAS-Mut7) spike in complex with TXG-0078 Fab -Conformation 1
type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2

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Macromolecule #1: SARS-CoV-2 spike (HP-GSAS-Mut7)

MacromoleculeName: SARS-CoV-2 spike (HP-GSAS-Mut7) / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHAIHV SGTNGTKRFD NPVLPFNDGV YFASTEKSNI IRGWIFGTTL DSKTQSLLIV NNATNVVIKV CEFQFCNDPF LGVYYHKNNK SWMESEFRVY SSANNCTFEY ...String:
MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHAIHV SGTNGTKRFD NPVLPFNDGV YFASTEKSNI IRGWIFGTTL DSKTQSLLIV NNATNVVIKV CEFQFCNDPF LGVYYHKNNK SWMESEFRVY SSANNCTFEY VSQPFLMDLE GKQGNFKNLR EFVFKNIDGY FKIYSKHTPI NLVRDLPQGF SALEPLVDLP IGINITRFQT LLALHRSYLT PGDSSSGWTA GAAAYYVGYL QPRTFLLKYN ENGTITDAVD CALDPLSETK CTLKSFTVEK GIYQTSNFRV QPTESIVRFP NITNLCPFGE VFNATRFASV YAWNRKRISN CVADYSVLYN SASFSTFKCY GVSPTKLNDL CFTNVYADSF VIRGDEVRQI APGQTGKIAD YNYKLPDDFT GCVIAWNSNN LDSKVGGNYN YLYRLFRKSN LKPFERDIST EIYQAGSTPC NGVEGFNCYF PLQSYGFQPT NGVGYQPYRV VVLSFELLHA PATVCGPKKS TNLVKNKCVN FNFNGLTGTG VLTESNKKFL PFQQFGRDIA DTTDAVRDPQ TLEILDITPC SFGGVSVITP GTNTSNQVAV LYQDVNCTEV PVAIHADQLT PTWRVYSTGS NVFQTRAGCL IGAEHVNNSY ECDIPIGAGI CASYQTQTNS PGSASSVASQ SIIAYTMSLG AENSCAYSNN SIAIPTNFTI SVTTEILPVS MTKTSVDCTM YICGDSTECS NLLLQYGSFC TQLNRALTGI AVEQDKNTQE VFAQVKQIYK TPPIKDFGGF NFSQILPDPS KPSKRSPIED LLFNKVTLAD AGFIKQYGDC LGDIAARDLI CAQKFNGLTV LPPLLTDEMI AQYTSALLAG TICSGWTFGA GPALQIPFPM QMAYRFNGIG VTQNVLYENQ KLIANQFNSA IGKIQDSLSS TPSALGKLQD VVNQNAQALN TLVKQLSSNF GAISSVLNDI LSRLDPPEAE VQIDRLITGR LQSLQTYVTQ QLIRAAEIRA SANLAATKMS ECVLGQSKRV DFCGKGYHLM SFPQSAPHGV VFLHVTYVPA QEKNFTTAPA ICHDGKAHFP REGVFVSNGT HWFVTQRNFY EPQIITTDNT FVSGNCDVVI GIVNNTVYDP LQPELDSFKE ELDKYFKNHT SPDVDLGDIS GINASVVNIQ KEIDRLNEVA KNLNESLIDL QELGKYEQGS GYIPEAPRDG QAYVRKDGEW VLLSTFLGRS LEVLFQGPGS AWSHPQFEKG GGSGGGGSGG SAWSHPQFEK

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration1 mg/mL
BufferpH: 7.4
Component:
ConcentrationFormulaName
50.0 mMTris-ClTris Chloride
150.0 mMNaClSodium Chloride

Details: 1X TBS
GridModel: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Pretreatment - Type: PLASMA CLEANING / Pretreatment - Time: 10 sec.
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 283 K / Instrument: FEI VITROBOT MARK IV
DetailsThe 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.

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Electron microscopy

MicroscopeTFS GLACIOS
Image recordingFilm or detector model: TFS FALCON 4i (4k x 4k) / Detector mode: COUNTING / Number grids imaged: 1 / Number real images: 4257 / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination 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 stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN

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Image processing

Startup modelType of model: OTHER
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Algorithm: BACK PROJECTION / Resolution.type: BY AUTHOR / Resolution: 3.17 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 3.1) / Number images used: 110482
Initial angle assignmentType: PROJECTION MATCHING / Software - Name: RELION (ver. 3.1)
Final angle assignmentType: ANGULAR RECONSTITUTION / Software - Name: RELION (ver. 3.1)
Final 3D classificationSoftware - Name: RELION (ver. 3.1)
FSC plot (resolution estimation)

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