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- EMDB-27038: N332-GT2 trimer in complex with pooled polyclonal fab from BG18-e... -

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Basic information

Entry
Database: EMDB / ID: EMD-27038
TitleN332-GT2 trimer in complex with pooled polyclonal fab from BG18-exposed mice (day 42)
Map datarefined map of N332-GT2 trimer in complex with pooled polyclonal fab from BG18-exposed mice (day 42)
Sample
  • Complex: N332-GT2 trimer in complex with pooled polyclonal fab from wild type mice (d42)
    • Complex: N332-GT2 trimer
    • Complex: pooled polyclonal fab from BG18-exposed mice (d42)
Biological speciesHuman immunodeficiency virus / Mus musculus (house mouse)
Methodsingle particle reconstruction / negative staining / Resolution: 25.0 Å
AuthorsJackson AM / Nogal B / Ward AB
Funding support United States, 4 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI144462 United States
Bill & Melinda Gates FoundationINV-002916 United States
Bill & Melinda Gates FoundationOPP1196345 United States
Bill & Melinda Gates FoundationINV-008813 United States
CitationJournal: Immunity / Year: 2022
Title: Antibodies from primary humoral responses modulate the recruitment of naive B cells during secondary responses.
Authors: Jeroen M J Tas / Ja-Hyun Koo / Ying-Cing Lin / Zhenfei Xie / Jon M Steichen / Abigail M Jackson / Blake M Hauser / Xuesong Wang / Christopher A Cottrell / Jonathan L Torres / John E Warner / ...Authors: Jeroen M J Tas / Ja-Hyun Koo / Ying-Cing Lin / Zhenfei Xie / Jon M Steichen / Abigail M Jackson / Blake M Hauser / Xuesong Wang / Christopher A Cottrell / Jonathan L Torres / John E Warner / Kathrin H Kirsch / Stephanie R Weldon / Bettina Groschel / Bartek Nogal / Gabriel Ozorowski / Sandhya Bangaru / Nicole Phelps / Yumiko Adachi / Saman Eskandarzadeh / Michael Kubitz / Dennis R Burton / Daniel Lingwood / Aaron G Schmidt / Usha Nair / Andrew B Ward / William R Schief / Facundo D Batista /
Abstract: Vaccines generate high-affinity antibodies by recruiting antigen-specific B cells to germinal centers (GCs), but the mechanisms governing the recruitment to GCs on secondary challenges remain unclear. ...Vaccines generate high-affinity antibodies by recruiting antigen-specific B cells to germinal centers (GCs), but the mechanisms governing the recruitment to GCs on secondary challenges remain unclear. Here, using preclinical SARS-CoV and HIV mouse models, we demonstrated that the antibodies elicited during primary humoral responses shaped the naive B cell recruitment to GCs during secondary exposures. The antibodies from primary responses could either enhance or, conversely, restrict the GC participation of naive B cells: broad-binding, low-affinity, and low-titer antibodies enhanced recruitment, whereas, by contrast, the high titers of high-affinity, mono-epitope-specific antibodies attenuated cognate naive B cell recruitment. Thus, the directionality and intensity of that effect was determined by antibody concentration, affinity, and epitope specificity. Circulating antibodies can, therefore, be important determinants of antigen immunogenicity. Future vaccines may need to overcome-or could, alternatively, leverage-the effects of circulating primary antibodies on subsequent naive B cell recruitment.
History
DepositionMay 20, 2022-
Header (metadata) releaseSep 7, 2022-
Map releaseSep 7, 2022-
UpdateOct 26, 2022-
Current statusOct 26, 2022Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_27038.map.gz / Format: CCP4 / Size: 27 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationrefined map of N332-GT2 trimer in complex with pooled polyclonal fab from BG18-exposed mice (day 42)
Voxel sizeX=Y=Z: 1.77 Å
Density
Contour LevelBy AUTHOR: 0.015
Minimum - Maximum-0.04075313 - 0.06461438
Average (Standard dev.)8.405759e-05 (±0.0042065578)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions192192192
Spacing192192192
CellA=B=C: 339.84 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: half map of N332-GT2 trimer in complex with...

Fileemd_27038_half_map_1.map
Annotationhalf map of N332-GT2 trimer in complex with pooled polyclonal fab from BG18-exposed mice (day 42)
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: half map of N332-GT2 trimer in complex with...

Fileemd_27038_half_map_2.map
Annotationhalf map of N332-GT2 trimer in complex with pooled polyclonal fab from BG18-exposed mice (day 42)
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire : N332-GT2 trimer in complex with pooled polyclonal fab from wild t...

EntireName: N332-GT2 trimer in complex with pooled polyclonal fab from wild type mice (d42)
Components
  • Complex: N332-GT2 trimer in complex with pooled polyclonal fab from wild type mice (d42)
    • Complex: N332-GT2 trimer
    • Complex: pooled polyclonal fab from BG18-exposed mice (d42)

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Supramolecule #1: N332-GT2 trimer in complex with pooled polyclonal fab from wild t...

SupramoleculeName: N332-GT2 trimer in complex with pooled polyclonal fab from wild type mice (d42)
type: complex / Chimera: Yes / ID: 1 / Parent: 0

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Supramolecule #2: N332-GT2 trimer

SupramoleculeName: N332-GT2 trimer / type: complex / Chimera: Yes / ID: 2 / Parent: 1
Source (natural)Organism: Human immunodeficiency virus
Recombinant expressionOrganism: Homo sapiens (human)

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Supramolecule #3: pooled polyclonal fab from BG18-exposed mice (d42)

SupramoleculeName: pooled polyclonal fab from BG18-exposed mice (d42) / type: complex / Chimera: Yes / ID: 3 / Parent: 1
Source (natural)Organism: Mus musculus (house mouse)
Recombinant expressionOrganism: Homo sapiens (human)

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Experimental details

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Structure determination

Methodnegative staining
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.4
StainingType: NEGATIVE / Material: uranyl formate

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Electron microscopy

MicroscopeFEI TECNAI F20
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm
Image recordingFilm or detector model: TVIPS TEMCAM-F416 (4k x 4k) / Average electron dose: 50.0 e/Å2
Experimental equipment
Model: Tecnai F20 / Image courtesy: FEI Company

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Image processing

Initial angle assignmentType: OTHER
Final angle assignmentType: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 25.0 Å / Resolution method: FSC 0.5 CUT-OFF / Number images used: 76912

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