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- EMDB-46824: Polyclonal immune complex of human subject 321-2006 Fab binding H1 HA -

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Basic information

Entry
Database: EMDB / ID: EMD-46824
TitlePolyclonal immune complex of human subject 321-2006 Fab binding H1 HA
Map dataNegative stain map of global refinement of particle stack used to sort polyclonal responses to H1 HA from human subject 321-2006
Sample
  • Complex: Polyclonal immune complex of human subject 321-2006 Fab binding H1 HA
Keywordsinfluenza / hemagglutinin / H1 / polyclonal / complex / Fab complex / viral fusion protein / VIRAL PROTEIN
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / negative staining / Resolution: 20.0 Å
AuthorsHan J / Rodriguez AJ / Ferguson JA / Ward AB
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)75N93019C00051 United States
CitationJournal: bioRxiv / Year: 2025
Title: Functional, Immunogenetic, and Structural Convergence in Influenza Immunity between Humans and Macaques.
Authors: Maya Sangesland / Ning Li / Yaroslav Tsybovsky / Megan D Rodgers / Julianna Han / Alesandra J Rodriguez / James A Ferguson / Amy R Henry / Sarah C Smith / Jesmine Roberts-Torres / Rebecca A ...Authors: Maya Sangesland / Ning Li / Yaroslav Tsybovsky / Megan D Rodgers / Julianna Han / Alesandra J Rodriguez / James A Ferguson / Amy R Henry / Sarah C Smith / Jesmine Roberts-Torres / Rebecca A Gillespie / Cuiping Liu / Jonah S Merriam / Tyler Stephens / Connor Williams / Emma Maestle / Martin Corcoran / Michelle Ravichandran / Adrian Creanga / Sarah F Andrews / Theodore C Pierson / Gunilla B Karlsson Hedestam / Chaim A Schramm / Douglas S Reed / Daniel C Douek / Tongqing Zhou / Andrew B Ward / Masaru Kanekiyo
Abstract: Human B cell immunity to the influenza hemagglutinin (HA) stem region, a universal influenza vaccine target, is often stereotyped and immunogenetically restricted, posing challenges for study outside ...Human B cell immunity to the influenza hemagglutinin (HA) stem region, a universal influenza vaccine target, is often stereotyped and immunogenetically restricted, posing challenges for study outside humans. Here, we show that macaques vaccinated with a HA stem immunogen elicit human-like public B cell lineages targeting two major conserved sites of vulnerability, the central stem and anchor epitopes. Central stem antibodies were predominantly derived from V 1-138, the macaque homolog of human V 1-69, a V -gene preferentially used in human central stem broadly neutralizing antibodies (bnAbs). Similarly, macaques produced anchor bnAbs with the human-like NWP motif. Both bnAb lineages were functionally and structurally analogous to their human counterparts, with recognition mediated largely by germline-encoded motifs. Thus the macaque immunoglobulin repertoire supports human-like public bnAb responses to influenza HA. Moreover, this underscores the utility of homologous germline-encoded immunity, suggesting that immune repertoires of macaques and humans may have been similarly shaped during evolution.
HIGHLIGHTS: Functional human-like public antibody lineages can be elicited to HA stem supersites in macaques. Macaque central stem bnAbs are predominantly derived from V 1-138, a V -gene homologous ...HIGHLIGHTS: Functional human-like public antibody lineages can be elicited to HA stem supersites in macaques. Macaque central stem bnAbs are predominantly derived from V 1-138, a V -gene homologous to human V 1-69. The human-like CDR L3 NWP anchor epitope-targeting lineage can be elicited in macaques.Central stem and anchor bnAbs from humans and macaques engage their respective epitopes with atomic level similarity.
History
DepositionSep 2, 2024-
Header (metadata) releaseJul 30, 2025-
Map releaseJul 30, 2025-
UpdateJul 30, 2025-
Current statusJul 30, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_46824.png

Downloads & links

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Map

FileDownload / File: emd_46824.map.gz / Format: CCP4 / Size: 34.3 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationNegative stain map of global refinement of particle stack used to sort polyclonal responses to H1 HA from human subject 321-2006
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
2.06 Å/pix.
x 208 pix.
= 428.48 Å		2.06 Å/pix.
x 208 pix.
= 428.48 Å		2.06 Å/pix.
x 208 pix.
= 428.48 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 2.06 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.024
Minimum - Maximum-0.028498739 - 0.09921919
Average (Standard dev.)0.00011520958 (±0.0037113084)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions208208208
Spacing208208208
CellA=B=C: 428.47998 Å
α=β=γ: 90.0 °

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Supplemental data

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Additional map: Negative stain map of polyclonal Fab binding the...

Fileemd_46824_additional_1.map
AnnotationNegative stain map of polyclonal Fab binding the H1 HA low stem epitope from human subject 321-2006
Projections & Slices
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Histogram (log scale)

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Additional map: Negative stain map of polyclonal Fab binding the...

Fileemd_46824_additional_2.map
AnnotationNegative stain map of polyclonal Fab binding the H1 HA central stem epitope from human subject 321-2006
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Additional map: Negative stain map of polyclonal Fab binding the...

Fileemd_46824_additional_3.map
AnnotationNegative stain map of polyclonal Fab binding the H1 HA anchor epitope from human subject 321-2006
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: Negative stain half map B for global refinement...

Fileemd_46824_half_map_1.map
AnnotationNegative stain half map B for global refinement of particle stack used to sort polyclonal responses to H1 HA from human subject 321-2006
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: Negative stain half map A for global refinement...

Fileemd_46824_half_map_2.map
AnnotationNegative stain half map A for global refinement of particle stack used to sort polyclonal responses to H1 HA from human subject 321-2006
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Polyclonal immune complex of human subject 321-2006 Fab binding H1 HA

EntireName: Polyclonal immune complex of human subject 321-2006 Fab binding H1 HA
Components
  • Complex: Polyclonal immune complex of human subject 321-2006 Fab binding H1 HA

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Supramolecule #1: Polyclonal immune complex of human subject 321-2006 Fab binding H1 HA

SupramoleculeName: Polyclonal immune complex of human subject 321-2006 Fab binding H1 HA
type: complex / ID: 1 / Parent: 0
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 280 KDa

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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

Concentration0.015 mg/mL
BufferpH: 7.4
StainingType: NEGATIVE / Material: 2% w/v uranyl formate
GridModel: Homemade / Material: COPPER / Mesh: 400 / Support film - Material: CARBON / Pretreatment - Type: GLOW DISCHARGE

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Electron microscopy

MicroscopeFEI TECNAI SPIRIT
Image recordingFilm or detector model: FEI EAGLE (4k x 4k) / Average electron dose: 25.0 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: LAB6
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: DARK FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.5 µm
Sample stageSpecimen holder model: SIDE ENTRY, EUCENTRIC / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Tecnai Spirit / Image courtesy: FEI Company

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Image processing

CTF correctionType: NONE
Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

4m4y

Final reconstructionResolution.type: BY AUTHOR / Resolution: 20.0 Å / Resolution method: FSC 0.5 CUT-OFF / Software - Name: RELION (ver. 3.0) / Number images used: 28815
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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