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- EMDB-61568: human GM-CSF with Fabs from autoantibodies, F1 and BD. -

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Basic information

Entry
Database: EMDB / ID: EMD-61568
Titlehuman GM-CSF with Fabs from autoantibodies, F1 and BD.
Map data
Sample
  • Complex: the complex of human GM-CSF with Fabs from its autoantibodies, F1 and BD.
    • Complex: human GM-CSF
    • Complex: F1 autoantibody for human GM-CSF
    • Complex: BD autoantibody for human GM-CSF
KeywordsAutoimmune pulmonary alveolar proteinosis / autoantibody / IMMUNE SYSTEM
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 4.0 Å
AuthorsKishikawa J / Kato T / Kurosaki T / Inoue T
Funding support Japan, 2 items
OrganizationGrant numberCountry
Japan Society for the Promotion of Science (JSPS)23K07625 Japan
Other private26-2-40 Japan
CitationJournal: Nat Commun / Year: 2026
Title: Affinity- and epitope-dependent pathogenicity of GM-CSF autoantibodies in patients with autoimmune pulmonary alveolar proteinosis.
Authors: Shinji Futami / Chie Kawai / Jun-Ichi Kishikawa / Masaki Hirose / Hiroshi Kida / Po-Hung Wang / Kazuo Yamashita / Fumihiko Ishikawa / Takayuki Kato / Yoshikazu Inoue / Atsushi Kumanogoh / ...Authors: Shinji Futami / Chie Kawai / Jun-Ichi Kishikawa / Masaki Hirose / Hiroshi Kida / Po-Hung Wang / Kazuo Yamashita / Fumihiko Ishikawa / Takayuki Kato / Yoshikazu Inoue / Atsushi Kumanogoh / Tomohiro Kurosaki / Takeshi Inoue /
Abstract: Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare lung disease caused by autoantibodies targeting granulocyte-macrophage colony-stimulating factor (GM-CSF). Although serum GM-CSF ...Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare lung disease caused by autoantibodies targeting granulocyte-macrophage colony-stimulating factor (GM-CSF). Although serum GM-CSF autoantibody levels are markedly increased in aPAP patients, total antibody titer does not correlate with disease severity. Here, we characterize 186 monoclonal anti-GM-CSF autoantibodies derived from GM-CSF-specific B cells in 28 aPAP patients with varying disease severity, including three longitudinal cohorts, to determine whether epitope specificity and affinity of the autoantibodies contribute to disease pathophysiology. We classify these antibodies into two groups based on their epitopes: class 1 (targeting A, BD, or D epitopes) and class 2 (targeting B or C epitopes). In class 1 antibodies, affinity strongly correlates with neutralization activity, whereas this relationship is weak or absent in class 2 antibodies. High-affinity class 1 antibodies are present at higher levels in patients with more severe disease and are sufficient to induce PAP symptoms in a humanized mouse model. Thus, these findings identify epitope specificity and affinity as key determinants of pathogenicity and provide a mechanistic framework for understanding why total serum autoantibody levels fail to reflect disease severity in aPAP.
History
DepositionSep 17, 2024-
Header (metadata) releaseMar 25, 2026-
Map releaseMar 25, 2026-
UpdateOct 7, 2026-
Current statusOct 7, 2026Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

emd_61568.png

Downloads & links

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Map

FileDownload / File: emd_61568.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
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AxesZ (Sec.)Y (Row.)X (Col.)
1.01 Å/pix.
x 300 pix.
= 303.75 Å		1.01 Å/pix.
x 300 pix.
= 303.75 Å		1.01 Å/pix.
x 300 pix.
= 303.75 Å

Surface

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Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.0125 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.5
Minimum - Maximum-2.3641918 - 3.5795176
Average (Standard dev.)-0.0012752231 (±0.05820801)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions300300300
Spacing300300300
CellA=B=C: 303.75 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_61568_msk_1.map
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AxesZYX

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Half map: #1

Fileemd_61568_half_map_1.map
Projections & Slices
AxesZYX

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Histogram

Histogram (log scale)

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Half map: #2

Fileemd_61568_half_map_2.map
Projections & Slices
AxesZYX

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Slices (1/2)
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Histogram (log scale)

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Sample components

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Entire : the complex of human GM-CSF with Fabs from its autoantibodies, F1...

EntireName: the complex of human GM-CSF with Fabs from its autoantibodies, F1 and BD.
Components
  • Complex: the complex of human GM-CSF with Fabs from its autoantibodies, F1 and BD.
    • Complex: human GM-CSF
    • Complex: F1 autoantibody for human GM-CSF
    • Complex: BD autoantibody for human GM-CSF

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Supramolecule #1: the complex of human GM-CSF with Fabs from its autoantibodies, F1...

SupramoleculeName: the complex of human GM-CSF with Fabs from its autoantibodies, F1 and BD.
type: complex / ID: 1 / Parent: 0
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 50 kDa/nm

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Supramolecule #2: human GM-CSF

SupramoleculeName: human GM-CSF / type: complex / ID: 2 / Parent: 1
Source (natural)Organism: Homo sapiens (human)

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Supramolecule #3: F1 autoantibody for human GM-CSF

SupramoleculeName: F1 autoantibody for human GM-CSF / type: complex / ID: 3 / Parent: 1
Source (natural)Organism: Homo sapiens (human)

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Supramolecule #4: BD autoantibody for human GM-CSF

SupramoleculeName: BD autoantibody for human GM-CSF / type: complex / ID: 4 / Parent: 1
Source (natural)Organism: 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

Concentration0.2 mg/mL
BufferpH: 7.5
GridModel: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 30 sec. / Pretreatment - Atmosphere: AIR
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Specialist opticsEnergy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Number real images: 10764 / Average electron dose: 65.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 0.032 mm / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 105000
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Particle selectionNumber selected: 939335 / Details: topaz extraction
CTF correctionSoftware - Name: cryoSPARC (ver. 4.0.0) / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: INSILICO MODEL / In silico model: ab initio reconstruction job in cryosparc
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Algorithm: FOURIER SPACE / Resolution.type: BY AUTHOR / Resolution: 4.0 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 4.0.0) / Number images used: 50310
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 4.0.0)
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 4.0.0)
Final 3D classificationSoftware - Name: cryoSPARC (ver. 4.0.0)
FSC plot (resolution estimation)

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