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- EMDB-17362: Homotypic interacting B1 fab bound to Chondroitin Sulfate A -

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Basic information

Entry
Database: EMDB / ID: EMD-17362
TitleHomotypic interacting B1 fab bound to Chondroitin Sulfate A
Map data
Sample
  • Complex: B1 fabs bound to chondroitin sulphate A
    • Protein or peptide: B1 fab light
    • Protein or peptide: B1 fab heavy
KeywordsChondroitin Sulfate A / SUGAR BINDING PROTEIN
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.2 Å
AuthorsRaghavan SSR / Dagil R / Wang KT / Salanti A
Funding support Denmark, 3 items
OrganizationGrant numberCountry
Novo Nordisk FoundationNNF22OC0076055 Denmark
Novo Nordisk FoundationNNF21OC0068192 Denmark
The Carlsberg FoundationCF20-0045 Denmark
CitationJournal: Nat Commun / Year: 2024
Title: Tumor-agnostic cancer therapy using antibodies targeting oncofetal chondroitin sulfate.
Authors: Elena Ethel Vidal-Calvo / Anne Martin-Salazar / Swati Choudhary / Robert Dagil / Sai Sundar Rajan Raghavan / Lara Duvnjak / Mie Anemone Nordmaj / Thomas Mandel Clausen / Ann Skafte / Jan ...Authors: Elena Ethel Vidal-Calvo / Anne Martin-Salazar / Swati Choudhary / Robert Dagil / Sai Sundar Rajan Raghavan / Lara Duvnjak / Mie Anemone Nordmaj / Thomas Mandel Clausen / Ann Skafte / Jan Oberkofler / Kaituo Wang / Mette Ø Agerbæk / Caroline Løppke / Amalie Mundt Jørgensen / Daria Ropac / Joana Mujollari / Shona Willis / Agnès Garcias López / Rebecca Louise Miller / Richard Torbjörn Gustav Karlsson / Felix Goerdeler / Yen-Hsi Chen / Ana R Colaço / Yong Wang / Thomas Lavstsen / Agnieszka Martowicz / Irina Nelepcu / Mona Marzban / Htoo Zarni Oo / Maj Sofie Ørum-Madsen / Yuzhuo Wang / Morten A Nielsen / Henrik Clausen / Michael Wierer / Dominik Wolf / Ismail Gögenur / Thor G Theander / Nader Al-Nakouzi / Tobias Gustavsson / Mads Daugaard / Ali Salanti /
Abstract: Molecular similarities between embryonic and malignant cells can be exploited to target tumors through specific signatures absent in healthy adult tissues. One such embryonic signature tumors express ...Molecular similarities between embryonic and malignant cells can be exploited to target tumors through specific signatures absent in healthy adult tissues. One such embryonic signature tumors express is oncofetal chondroitin sulfate (ofCS), which supports disease progression and dissemination in cancer. Here, we report the identification and characterization of phage display-derived antibody fragments recognizing two distinct ofCS epitopes. These antibody fragments show binding affinity to ofCS in the low nanomolar range across a broad selection of solid tumor types in vitro and in vivo with minimal binding to normal, inflamed, or benign tumor tissues. Anti-ofCS antibody drug conjugates and bispecific immune cell engagers based on these targeting moieties disrupt tumor progression in animal models of human and murine cancers. Thus, anti-ofCS antibody fragments hold promise for the development of broadly effective therapeutic and diagnostic applications targeting human malignancies.
History
DepositionMay 16, 2023-
Header (metadata) releaseJun 5, 2024-
Map releaseJun 5, 2024-
UpdateJul 2, 2025-
Current statusJul 2, 2025Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

emd_17362.png

Downloads & links

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Map

FileDownload / File: emd_17362.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 360 pix.
= 299.52 Å		0.83 Å/pix.
x 360 pix.
= 299.52 Å		0.83 Å/pix.
x 360 pix.
= 299.52 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.832 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.3
Minimum - Maximum-0.79359025 - 1.7457781
Average (Standard dev.)0.000762784 (±0.04181023)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions360360360
Spacing360360360
CellA=B=C: 299.52002 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_17362_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_17362_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : B1 fabs bound to chondroitin sulphate A

EntireName: B1 fabs bound to chondroitin sulphate A
Components
  • Complex: B1 fabs bound to chondroitin sulphate A
    • Protein or peptide: B1 fab light
    • Protein or peptide: B1 fab heavy

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Supramolecule #1: B1 fabs bound to chondroitin sulphate A

SupramoleculeName: B1 fabs bound to chondroitin sulphate A / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 50 kDa/nm

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Macromolecule #1: B1 fab light

MacromoleculeName: B1 fab light / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23.662383 KDa
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
SequenceString: MEVQLLESGG GLVQPGGSLR LSCAASGFTF TSYAMSWVRQ APGKGLEWVS GISYGSGDTY YADSVKGRFT ISRDNSKNTL YLQMNSLRA EDTAVYYCAR SRGSQTFDYW GQGTLVTVSS ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS W NSGALTSG ...String:
MEVQLLESGG GLVQPGGSLR LSCAASGFTF TSYAMSWVRQ APGKGLEWVS GISYGSGDTY YADSVKGRFT ISRDNSKNTL YLQMNSLRA EDTAVYYCAR SRGSQTFDYW GQGTLVTVSS ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS W NSGALTSG VHTFPAVLQS SGLYSLSSVV TVPSSSLGTQ TYICNVNHKP SNTKVDKKVE PKSEF

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Macromolecule #2: B1 fab heavy

MacromoleculeName: B1 fab heavy / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 26.419492 KDa
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
SequenceString: DIVLTQSPAT LSLSPGERAT LSCRASQSVS RSLAWYQQKP GQAPRLLIYG SSNRATGIPA RFSGSGSGTD FTLTISSLEP EDFAVYYCQ QRIHTSWTFG QGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS ...String:
DIVLTQSPAT LSLSPGERAT LSCRASQSVS RSLAWYQQKP GQAPRLLIYG SSNRATGIPA RFSGSGSGTD FTLTISSLEP EDFAVYYCQ QRIHTSWTFG QGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEAGKPI PNPLLGLDST GGSAHIVMVD AY KPTK

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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
Image recordingFilm or detector model: FEI FALCON III (4k x 4k) / Average electron dose: 40.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.8000000000000003 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: NONE
Startup modelType of model: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 1250000
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION

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