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- EMDB-26720: SJ25C1 Fab in complex with soluble CD19 -

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Basic information

Entry
Database: EMDB / ID: EMD-26720
TitleSJ25C1 Fab in complex with soluble CD19
Map dataSJ25C1 Fab in complex with soluble CD19
Sample
  • Complex: SJ25C1 Fab in complex with soluble CD19
    • Complex: B-lymphocyte antigen CD19
      • Protein or peptide: B-lymphocyte antigen CD19
    • Complex: SJ25C1 Fab light chain, SJ25C1 Fab heavy chain
      • Protein or peptide: SJ25C1 Fab light chain
      • Protein or peptide: SJ25C1 Fab heavy chain
KeywordsComplex / PROTEIN BINDING
Function / homology
Function and homology information


regulation of B cell activation / antigen receptor-mediated signaling pathway / B-1 B cell differentiation / regulation of B cell receptor signaling pathway / B cell proliferation involved in immune response / immunoglobulin mediated immune response / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / Regulation of Complement cascade / positive regulation of release of sequestered calcium ion into cytosol / B cell receptor signaling pathway ...regulation of B cell activation / antigen receptor-mediated signaling pathway / B-1 B cell differentiation / regulation of B cell receptor signaling pathway / B cell proliferation involved in immune response / immunoglobulin mediated immune response / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / Regulation of Complement cascade / positive regulation of release of sequestered calcium ion into cytosol / B cell receptor signaling pathway / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / Constitutive Signaling by Aberrant PI3K in Cancer / PIP3 activates AKT signaling / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / membrane raft / external side of plasma membrane / protein-containing complex / extracellular exosome / plasma membrane
Similarity search - Function
B-lymphocyte antigen CD19 / Immunoglobulin subtype / Immunoglobulin / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold
Similarity search - Domain/homology
B-lymphocyte antigen CD19
Similarity search - Component
Biological speciesHomo sapiens (human) / Mus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.4 Å
AuthorsMeyerson J / He C
Funding support1 items
OrganizationGrant numberCountry
Not funded
CitationJournal: Sci Immunol / Year: 2023
Title: CD19 CAR antigen engagement mechanisms and affinity tuning.
Authors: Changhao He / Jorge Mansilla-Soto / Nandish Khanra / Mohamad Hamieh / Victor Bustos / Alice J Paquette / Andreina Garcia Angus / Derek M Shore / William J Rice / George Khelashvili / Michel ...Authors: Changhao He / Jorge Mansilla-Soto / Nandish Khanra / Mohamad Hamieh / Victor Bustos / Alice J Paquette / Andreina Garcia Angus / Derek M Shore / William J Rice / George Khelashvili / Michel Sadelain / Joel R Meyerson /
Abstract: Chimeric antigen receptor (CAR) T cell therapy relies on T cells that are guided by synthetic receptors to target and lyse cancer cells. CARs bind to cell surface antigens through an scFv (binder), ...Chimeric antigen receptor (CAR) T cell therapy relies on T cells that are guided by synthetic receptors to target and lyse cancer cells. CARs bind to cell surface antigens through an scFv (binder), the affinity of which is central to determining CAR T cell function and therapeutic success. CAR T cells targeting CD19 were the first to achieve marked clinical responses in patients with relapsed/refractory B cell malignancies and to be approved by the U.S. Food and Drug Administration (FDA). We report cryo-EM structures of CD19 antigen with the binder FMC63, which is used in four FDA-approved CAR T cell therapies (Kymriah, Yescarta, Tecartus, and Breyanzi), and the binder SJ25C1, which has also been used extensively in multiple clinical trials. We used these structures for molecular dynamics simulations, which guided creation of lower- or higher-affinity binders, and ultimately produced CAR T cells endowed with distinct tumor recognition sensitivities. The CAR T cells exhibited different antigen density requirements to trigger cytolysis and differed in their propensity to prompt trogocytosis upon contacting tumor cells. Our work shows how structural information can be applied to tune CAR T cell performance to specific target antigen densities.
History
DepositionApr 22, 2022-
Header (metadata) releaseFeb 15, 2023-
Map releaseFeb 15, 2023-
UpdateMay 21, 2025-
Current statusMay 21, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_26720.png

Downloads & links

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Map

FileDownload / File: emd_26720.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationSJ25C1 Fab in complex with soluble CD19
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.86 Å/pix.
x 300 pix.
= 257.7 Å		0.86 Å/pix.
x 300 pix.
= 257.7 Å		0.86 Å/pix.
x 300 pix.
= 257.7 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.859 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.6
Minimum - Maximum-3.5633152 - 5.0001574
Average (Standard dev.)0.0007951497 (±0.059048977)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions300300300
Spacing300300300
CellA=B=C: 257.7 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: SJ25C1 Fab in complex with soluble CD19

Fileemd_26720_half_map_1.map
AnnotationSJ25C1 Fab in complex with soluble CD19
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: SJ25C1 Fab in complex with soluble CD19

Fileemd_26720_half_map_2.map
AnnotationSJ25C1 Fab in complex with soluble CD19
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : SJ25C1 Fab in complex with soluble CD19

EntireName: SJ25C1 Fab in complex with soluble CD19
Components
  • Complex: SJ25C1 Fab in complex with soluble CD19
    • Complex: B-lymphocyte antigen CD19
      • Protein or peptide: B-lymphocyte antigen CD19
    • Complex: SJ25C1 Fab light chain, SJ25C1 Fab heavy chain
      • Protein or peptide: SJ25C1 Fab light chain
      • Protein or peptide: SJ25C1 Fab heavy chain

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Supramolecule #1: SJ25C1 Fab in complex with soluble CD19

SupramoleculeName: SJ25C1 Fab in complex with soluble CD19 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all

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Supramolecule #2: B-lymphocyte antigen CD19

SupramoleculeName: B-lymphocyte antigen CD19 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

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Supramolecule #3: SJ25C1 Fab light chain, SJ25C1 Fab heavy chain

SupramoleculeName: SJ25C1 Fab light chain, SJ25C1 Fab heavy chain / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3
Source (natural)Organism: Mus musculus (house mouse)

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Macromolecule #1: B-lymphocyte antigen CD19

MacromoleculeName: B-lymphocyte antigen CD19 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 30.649246 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MPPPRLLFFL LFLTPMEVRP EEPLVVKVEE GDNAVLQCLK GTSDGPTQQL TWSRESPLKP FLKLSLGLPG LGIHVSPLAI WLFISNVSQ QMGGFYLCQP GPPSEKAWQP GWTVNVEGSG ELFRWNVSDL GGLGCGLKNR SSEGPSSPSG KLMSPKLYVW A KDRPEIWE ...String:
MPPPRLLFFL LFLTPMEVRP EEPLVVKVEE GDNAVLQCLK GTSDGPTQQL TWSRESPLKP FLKLSLGLPG LGIHVSPLAI WLFISNVSQ QMGGFYLCQP GPPSEKAWQP GWTVNVEGSG ELFRWNVSDL GGLGCGLKNR SSEGPSSPSG KLMSPKLYVW A KDRPEIWE GEPPCLPPRD SLNQSLSQDL TMAPGSTLWL SCGVPPDSVS RGPLSWTHVH PKGPKSLLSL ELKDDRPARD MW VMETGLL LPRATAQDAG KYYCHRGNLT MSFHLEITAR P

UniProtKB: B-lymphocyte antigen CD19

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Macromolecule #2: SJ25C1 Fab light chain

MacromoleculeName: SJ25C1 Fab light chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 25.765703 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MGWSCIILFL VATATGVHSD IELTQSPKFM STSVGDRVSV TCKASQNVGT NVAWYQQKPG QSPKPLIYSA TYRNSGVPDR FTGSGSGTD FTLTITNVQS KDLADYFCQQ YNRYPYTSGG GTKLEIKRTR TVAAPSVFIF PPSDEQLKSG TASVVCLLNN F YPREAKVQ ...String:
MGWSCIILFL VATATGVHSD IELTQSPKFM STSVGDRVSV TCKASQNVGT NVAWYQQKPG QSPKPLIYSA TYRNSGVPDR FTGSGSGTD FTLTITNVQS KDLADYFCQQ YNRYPYTSGG GTKLEIKRTR TVAAPSVFIF PPSDEQLKSG TASVVCLLNN F YPREAKVQ WKVDNALQSG NSQESVTEQD SKDSTYSLSS TLTLSKADYE KHKVYACEVT HQGLSSPVTK SFNRGEC

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Macromolecule #3: SJ25C1 Fab heavy chain

MacromoleculeName: SJ25C1 Fab heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 27.030293 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MGWSCIILFL VATATGVHSE VKLQQSGAEL VRPGSSVKIS CKASGYAFSS YWMNWVKQRP GQGLEWIGQI YPGDGDTNYN GKFKGQATL TADKSSSTAY MQLSGLTSED SAVYFCARKT ISSVVDFYFD YWGQGTTVTV SSASTKGPSV FPLAPSSKST S GGTAALGC ...String:
MGWSCIILFL VATATGVHSE VKLQQSGAEL VRPGSSVKIS CKASGYAFSS YWMNWVKQRP GQGLEWIGQI YPGDGDTNYN GKFKGQATL TADKSSSTAY MQLSGLTSED SAVYFCARKT ISSVVDFYFD YWGQGTTVTV SSASTKGPSV FPLAPSSKST S GGTAALGC LVKDYFPEPV TVSWNSGALT SGVHTFPAVL QSSGLYSLSS VVTVPSSSLG TQTYICNVNH KPSNTKVDKK VE PKSCHHH HHHHH

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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
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TALOS ARCTICA
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 53.47 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.4 µm / Nominal defocus min: 1.5 µm
Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 351934
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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