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- EMDB-41399: Antibody N3-1 bound to SARS-CoV-2 spike -

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Basic information

Entry
Database: EMDB / ID: EMD-41399
TitleAntibody N3-1 bound to SARS-CoV-2 spike
Map datasharpen map
Sample
  • Complex: Complex of N3-1 bound to SARS-CoV-2 spike
    • Complex: SARS-CoV-2 spike
      • Protein or peptide: SARS-CoV-2 spike
    • Complex: N3-1
      • Protein or peptide: N3-1 Fab heavy chain
      • Protein or peptide: N3-1 Fab light chain
KeywordsSARS-CoV-2 spike / neutralizing antibody / RBD-directed antibody / quaternary epitope / VIRAL PROTEIN
Biological speciesSevere acute respiratory syndrome coronavirus 2 / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.8 Å
AuthorsHsieh C-L / McLellan JS
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)R01 AI127521 United States
CitationJournal: Commun Biol / Year: 2023
Title: SARS-COV-2 Omicron variants conformationally escape a rare quaternary antibody binding mode.
Authors: Jule Goike / Ching-Lin Hsieh / Andrew P Horton / Elizabeth C Gardner / Ling Zhou / Foteini Bartzoka / Nianshuang Wang / Kamyab Javanmardi / Andrew Herbert / Shawn Abbassi / Xuping Xie / ...Authors: Jule Goike / Ching-Lin Hsieh / Andrew P Horton / Elizabeth C Gardner / Ling Zhou / Foteini Bartzoka / Nianshuang Wang / Kamyab Javanmardi / Andrew Herbert / Shawn Abbassi / Xuping Xie / Hongjie Xia / Pei-Yong Shi / Rebecca Renberg / Thomas H Segall-Shapiro / Cynthia I Terrace / Wesley Wu / Raghav Shroff / Michelle Byrom / Andrew D Ellington / Edward M Marcotte / James M Musser / Suresh V Kuchipudi / Vivek Kapur / George Georgiou / Scott C Weaver / John M Dye / Daniel R Boutz / Jason S McLellan / Jimmy D Gollihar /
Abstract: The ongoing evolution of SARS-CoV-2 into more easily transmissible and infectious variants has provided unprecedented insight into mutations enabling immune escape. Understanding how these mutations ...The ongoing evolution of SARS-CoV-2 into more easily transmissible and infectious variants has provided unprecedented insight into mutations enabling immune escape. Understanding how these mutations affect the dynamics of antibody-antigen interactions is crucial to the development of broadly protective antibodies and vaccines. Here we report the characterization of a potent neutralizing antibody (N3-1) identified from a COVID-19 patient during the first disease wave. Cryogenic electron microscopy revealed a quaternary binding mode that enables direct interactions with all three receptor-binding domains of the spike protein trimer, resulting in extraordinary avidity and potent neutralization of all major variants of concern until the emergence of Omicron. Structure-based rational design of N3-1 mutants improved binding to all Omicron variants but only partially restored neutralization of the conformationally distinct Omicron BA.1. This study provides new insights into immune evasion through changes in spike protein dynamics and highlights considerations for future conformationally biased multivalent vaccine designs.
History
DepositionJul 29, 2023-
Header (metadata) releaseJan 17, 2024-
Map releaseJan 17, 2024-
UpdateJan 17, 2024-
Current statusJan 17, 2024Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_41399.png

Downloads & links

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Map

FileDownload / File: emd_41399.map.gz / Format: CCP4 / Size: 307.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationsharpen map
Voxel sizeX=Y=Z: 1.1 Å
Density
Contour LevelBy AUTHOR: 1.8
Minimum - Maximum-6.6051984 - 14.207281999999999
Average (Standard dev.)-0.0033005786 (±0.19812821)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions432432432
Spacing432432432
CellA=B=C: 475.2 Å
α=β=γ: 90.0 °

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Supplemental data

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Additional map: map

Fileemd_41399_additional_1.map
Annotationmap
Projections & Slices
AxesZYX

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Additional map: DeepEMhancer map

Fileemd_41399_additional_2.map
AnnotationDeepEMhancer map
Projections & Slices
AxesZYX

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Histogram

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Additional map: Composite map

Fileemd_41399_additional_3.map
AnnotationComposite map
Projections & Slices
AxesZYX

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Histogram

Histogram (log scale)

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Half map: half map

Fileemd_41399_half_map_1.map
Annotationhalf map
Projections & Slices
AxesZYX

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Slices (1/2)
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Histogram

Histogram (log scale)

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Half map: half map

Fileemd_41399_half_map_2.map
Annotationhalf map
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AxesZYX

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Sample components

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Entire : Complex of N3-1 bound to SARS-CoV-2 spike

EntireName: Complex of N3-1 bound to SARS-CoV-2 spike
Components
  • Complex: Complex of N3-1 bound to SARS-CoV-2 spike
    • Complex: SARS-CoV-2 spike
      • Protein or peptide: SARS-CoV-2 spike
    • Complex: N3-1
      • Protein or peptide: N3-1 Fab heavy chain
      • Protein or peptide: N3-1 Fab light chain

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Supramolecule #1: Complex of N3-1 bound to SARS-CoV-2 spike

SupramoleculeName: Complex of N3-1 bound to SARS-CoV-2 spike / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all

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Supramolecule #2: SARS-CoV-2 spike

SupramoleculeName: SARS-CoV-2 spike / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2

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Supramolecule #3: N3-1

SupramoleculeName: N3-1 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: SARS-CoV-2 spike

MacromoleculeName: SARS-CoV-2 spike / type: protein_or_peptide / ID: 1 / Enantiomer: DEXTRO
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MFVFLVLLPL VSSQCVNLT T RTQLPPAY TN SFTRGVY YPD KVFRSS VLHS TQDLF LPFFS NVTW FHAIHV SGT NGTKRFD NP VLPFNDGV Y FASTEKSNI IRGWIFGTTL DSKTQSLLI V NNATNVVI KV CEFQFCN DPF LGVYYH KNNK SWMES ...String:
MFVFLVLLPL VSSQCVNLT T RTQLPPAY TN SFTRGVY YPD KVFRSS VLHS TQDLF LPFFS NVTW FHAIHV SGT NGTKRFD NP VLPFNDGV Y FASTEKSNI IRGWIFGTTL DSKTQSLLI V NNATNVVI KV CEFQFCN DPF LGVYYH KNNK SWMES EFRVY SSAN NCTFEY VSQ PFLMDLE GK QGNFKNLR E FVFKNIDGY FKIYSKHTPI NLVRDLPQG F SALEPLVD LP IGINITR FQT LLALHR SYLT PGDSS SGWTA GAAA YYVGYL QPR TFLLKYN EN GTITDAVD C ALDPLSETK CTLKSFTVEK GIYQTSNFR V QPTESIVR FP NITNLCP FGE VFNATR FASV YAWNR KRISN CVAD YSVLYN SAS FSTFKCY GV SPTKLNDL C FTNVYADSF VIRGDEVRQI APGQTGKIA D YNYKLPDD FT GCVIAWN SNN LDSKVG GNYN YLYRL FRKSN LKPF ERDIST EIY QAGSTPC NG VEGFNCYF P LQSYGFQPT NGVGYQPYRV VVLSFELLH A PATVCGPK KS TNLVKNK CVN FNFNGL TGTG VLTES NKKFL PFQQ FGRDIA DTT DAVRDPQ TL EILDITPC S FGGVSVITP GTNTSNQVAV LYQDVNCTE V PVAIHADQ LT PTWRVYS TGS NVFQTR AGCL IGAEH VNNSY ECDI PIGAGI CAS YQTQTNS PG SASSVASQ S IIAYTMSLG AENSVAYSNN SIAIPTNFT I SVTTEILP VS MTKTSVD CTM YICGDS TECS NLLLQ YGSFC TQLN RALTGI AVE QDKNTQE VF AQVKQIYK T PPIKDFGGF NFSQILPDPS KPSKRSPIE D LLFNKVTL AD AGFIKQY GDC LGDIAA RDLI CAQKF NGLTV LPPL LTDEMI AQY TSALLAG TI TSGWTFGA G PALQIPFPM QMAYRFNGIG VTQNVLYEN Q KLIANQFN SA IGKIQDS LSS TPSALG KLQD VVNQN AQALN TLVK QLSSNF GAI SSVLNDI LS RLDPPEAE V QIDRLITGR LQSLQTYVTQ QLIRAAEIR A SANLAATK MS ECVLGQS KRV DFCGKG YHLM SFPQS APHGV VFLH VTYVPA QEK NFTTAPA IC HDGKAHFP R EGVFVSNGT HWFVTQRNFY EPQIITTDN T FVSGNCDV VI GIVNNTV YDP LQPELD SFKE ELDKY FKNHT SPDV DLGDIS GIN ASVVNIQ KE IDRLNEVA K NLNESLIDL QELGKYEQGS GYIPEAPRD G QAYVRKDG EW VLLSTFL GRS LEVLFQ GPGH HHHHH HHSAW SHPQ FEKGGG SGG GGSGGSA WS HPQFEK

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Macromolecule #2: N3-1 Fab heavy chain

MacromoleculeName: N3-1 Fab heavy chain / type: protein_or_peptide / ID: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
QVQLQQWGPG LVNPSETLSL TCSVSGGSFA TENYYWSWIR QHPGEGLEWI GNIYFSGNTY YNPSLNNRFT ISFDTSKNHL SLKLPSVTAA DTAVYYCARG TIYFDRSGYR RVDPFHIWGQ GTMVIVSS

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Macromolecule #3: N3-1 Fab light chain

MacromoleculeName: N3-1 Fab light chain / type: protein_or_peptide / ID: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
DIQMTQSPST LSASVGDRVT ITCRASQSIS SWLAWYQQKP GKAPKLLIYD ASSLESGVPS RFSGSGSGTE FTLTISSLQP DDFATYYCQQ YNSYSPWTFG QGTKVEIK

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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

BufferpH: 8 / Details: 2 mM Tris pH 8.0, 200 mM NaCl, 0.02% NaN3
GridModel: UltrAuFoil R1.2/1.3 / Material: GOLD
VitrificationCryogen name: ETHANE
DetailsCollected on UltrAuFoil 1.2-1.3 with 0.2 mg/mL HexaPro and 5x fold molar excess FabN3-1 spiked in 30 minutes before freezing.

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.5 µm
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 80.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: NONE
Initial angle assignmentType: RANDOM ASSIGNMENT
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 266585

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