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- EMDB-26604: H1 Solomon Islands 2006 hemagglutinin in complex with Ab111 -

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Basic information

Entry
Database: EMDB / ID: EMD-26604
TitleH1 Solomon Islands 2006 hemagglutinin in complex with Ab111
Map datahemagglutinin H1 Solomon Islands 2006 in complex with Ab111
Sample
  • Complex: hemagglutinin H1 Solomon Islands/03/2006 in complex with ab109 Fab
    • Complex: Hemagglutinin
    • Complex: ab109 Fab heavy chain, ab 109 Fab light chain
Biological speciesInfluenza A virus (A/Solomon Islands/3/2006(H1N1)) / Mus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 5.0 Å
AuthorsWindsor IW / Caradonna TM / Schmidt AG
Funding support United States, 2 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)R01AI146779 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)P01AI089618 United States
CitationJournal: Cell Rep / Year: 2022
Title: An epitope-enriched immunogen expands responses to a conserved viral site.
Authors: Timothy M Caradonna / Larance Ronsard / Ashraf S Yousif / Ian W Windsor / Rachel Hecht / Thalia Bracamonte-Moreno / Anne A Roffler / Max J Maron / Daniel P Maurer / Jared Feldman / Elisa ...Authors: Timothy M Caradonna / Larance Ronsard / Ashraf S Yousif / Ian W Windsor / Rachel Hecht / Thalia Bracamonte-Moreno / Anne A Roffler / Max J Maron / Daniel P Maurer / Jared Feldman / Elisa Marchiori / Ralston M Barnes / Daniel Rohrer / Nils Lonberg / Thomas H Oguin / Gregory D Sempowski / Thomas B Kepler / Masayuki Kuraoka / Daniel Lingwood / Aaron G Schmidt /
Abstract: Pathogens evade host humoral responses by accumulating mutations in surface antigens. While variable, there are conserved regions that cannot mutate without compromising fitness. Antibodies targeting ...Pathogens evade host humoral responses by accumulating mutations in surface antigens. While variable, there are conserved regions that cannot mutate without compromising fitness. Antibodies targeting these conserved epitopes are often broadly protective but remain minor components of the repertoire. Rational immunogen design leverages a structural understanding of viral antigens to modulate humoral responses to favor these responses. Here, we report an epitope-enriched immunogen presenting a higher copy number of the influenza hemagglutinin (HA) receptor-binding site (RBS) epitope relative to other B cell epitopes. Immunization in a partially humanized murine model imprinted with an H1 influenza shows H1-specific serum and >99% H1-specific B cells being RBS-directed. Single B cell analyses show a genetically restricted response that structural analysis defines as RBS-directed antibodies engaging the RBS with germline-encoded contacts. These data show how epitope enrichment expands B cell responses toward conserved epitopes and advances immunogen design approaches for next-generation viral vaccines.
History
DepositionApr 7, 2022-
Header (metadata) releaseNov 23, 2022-
Map releaseNov 23, 2022-
UpdateNov 23, 2022-
Current statusNov 23, 2022Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_26604.map.gz / Format: CCP4 / Size: 3.8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationhemagglutinin H1 Solomon Islands 2006 in complex with Ab111
Voxel sizeX=Y=Z: 2.475 Å
Density
Contour LevelBy AUTHOR: 0.05
Minimum - Maximum-0.2476559 - 0.40672743
Average (Standard dev.)0.0009778999 (±0.01500516)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions100100100
Spacing100100100
CellA=B=C: 247.49998 Å
α=β=γ: 90.0 °

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Supplemental data

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Sample components

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Entire : hemagglutinin H1 Solomon Islands/03/2006 in complex with ab109 Fab

EntireName: hemagglutinin H1 Solomon Islands/03/2006 in complex with ab109 Fab
Components
  • Complex: hemagglutinin H1 Solomon Islands/03/2006 in complex with ab109 Fab
    • Complex: Hemagglutinin
    • Complex: ab109 Fab heavy chain, ab 109 Fab light chain

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Supramolecule #1: hemagglutinin H1 Solomon Islands/03/2006 in complex with ab109 Fab

SupramoleculeName: hemagglutinin H1 Solomon Islands/03/2006 in complex with ab109 Fab
type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1-#3

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Supramolecule #2: Hemagglutinin

SupramoleculeName: Hemagglutinin / type: complex / Chimera: Yes / ID: 2 / Parent: 1 / Macromolecule list: #1
Source (natural)Organism: Influenza A virus (A/Solomon Islands/3/2006(H1N1))
Recombinant expressionOrganism: Trichoplusia ni (cabbage looper)

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Supramolecule #3: ab109 Fab heavy chain, ab 109 Fab light chain

SupramoleculeName: ab109 Fab heavy chain, ab 109 Fab light chain / type: complex / Chimera: Yes / ID: 3 / Parent: 1 / Macromolecule list: #2-#3
Source (natural)Organism: Mus musculus (house mouse)
Recombinant expressionOrganism: Homo sapiens (human)

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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: 7.5
VitrificationCryogen name: ETHANE

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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
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 1.07 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionSoftware - Name: CTFFIND
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: RELION
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: RELION
Final reconstructionApplied symmetry - Point group: C3 (3 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 5.0 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 3.1.2) / Number images used: 179737
FSC plot (resolution estimation)

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