[English] 日本語
Yorodumi
- EMDB-71704: HU-38 Fab with PRAME pMHC -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-71704
TitleHU-38 Fab with PRAME pMHC
Map data
Sample
  • Complex: complex of HU38 Fab with PRAME pMHC and anti-Kappa VHH
    • Protein or peptide: MHC class I antigen
    • Protein or peptide: VHH antibody
    • Protein or peptide: PRAME peptide
    • Protein or peptide: HU-38 Heavy Chain
    • Protein or peptide: Beta-2-microglobulin
    • Protein or peptide: HU-38 Light Chain
  • Ligand: water
KeywordsPRAME / pMHC / PEPTIDE BINDING PROTEIN / PEPTIDE BINDING PROTEIN-IMMUNE SYSTEM complex
Function / homology
Function and homology information


antigen processing and presentation of peptide antigen via MHC class I / regulation of natural killer cell mediated immunity / early endosome lumen / Nef mediated downregulation of MHC class I complex cell surface expression / DAP12 interactions / antigen processing and presentation of exogenous peptide antigen via MHC class Ib / Endosomal/Vacuolar pathway / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / lumenal side of endoplasmic reticulum membrane / regulation of iron ion transport ...antigen processing and presentation of peptide antigen via MHC class I / regulation of natural killer cell mediated immunity / early endosome lumen / Nef mediated downregulation of MHC class I complex cell surface expression / DAP12 interactions / antigen processing and presentation of exogenous peptide antigen via MHC class Ib / Endosomal/Vacuolar pathway / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / lumenal side of endoplasmic reticulum membrane / regulation of iron ion transport / negative regulation of iron ion transport / negative regulation of forebrain neuron differentiation / peptide antigen assembly with MHC class I protein complex / ER to Golgi transport vesicle membrane / HFE-transferrin receptor complex / MHC class I peptide loading complex / transferrin transport / negative regulation of receptor-mediated endocytosis / cellular response to iron ion / positive regulation of T cell cytokine production / antigen processing and presentation of endogenous peptide antigen via MHC class I / MHC class I protein complex / peptide antigen assembly with MHC class II protein complex / negative regulation of epithelial cell proliferation / cellular response to nicotine / negative regulation of neurogenesis / MHC class II protein complex / positive regulation of receptor-mediated endocytosis / specific granule lumen / antigen processing and presentation of exogenous peptide antigen via MHC class II / positive regulation of immune response / peptide antigen binding / recycling endosome membrane / phagocytic vesicle membrane / positive regulation of T cell activation / Interferon gamma signaling / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / sensory perception of smell / Modulation by Mtb of host immune system / tertiary granule lumen / positive regulation of cellular senescence / MHC class II protein complex binding / DAP12 signaling / late endosome membrane / ER-Phagosome pathway / early endosome membrane / amyloid fibril formation / protein homotetramerization / intracellular iron ion homeostasis / learning or memory / immune response / endoplasmic reticulum lumen / Amyloid fiber formation / external side of plasma membrane / Golgi membrane / lysosomal membrane / focal adhesion / Neutrophil degranulation / SARS-CoV-2 activates/modulates innate and adaptive immune responses / structural molecule activity / Golgi apparatus / endoplasmic reticulum / protein homodimerization activity / : / extracellular exosome / extracellular region / membrane / identical protein binding / plasma membrane
Similarity search - Function
MHC class I alpha chain, alpha1 alpha2 domains / Class I Histocompatibility antigen, domains alpha 1 and 2 / Beta-2-Microglobulin / : / MHC class I-like antigen recognition-like / MHC class I-like antigen recognition-like superfamily / MHC classes I/II-like antigen recognition protein / : / Immunoglobulin/major histocompatibility complex, conserved site / Immunoglobulins and major histocompatibility complex proteins signature. ...MHC class I alpha chain, alpha1 alpha2 domains / Class I Histocompatibility antigen, domains alpha 1 and 2 / Beta-2-Microglobulin / : / MHC class I-like antigen recognition-like / MHC class I-like antigen recognition-like superfamily / MHC classes I/II-like antigen recognition protein / : / Immunoglobulin/major histocompatibility complex, conserved site / Immunoglobulins and major histocompatibility complex proteins signature. / Immunoglobulin C-Type / Immunoglobulin C1-set / Immunoglobulin C1-set domain / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold
Similarity search - Domain/homology
Beta-2-microglobulin / MHC class I antigen
Similarity search - Component
Biological speciesHomo sapiens (human) / Lama glama (llama) / Mus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.72 Å
AuthorsMortenson DE / Yu X
Funding support1 items
OrganizationGrant numberCountry
Not funded
CitationJournal: MAbs / Year: 2025
Title: Development of a PRAME pMHC targeted T cell engager for solid tumor therapy.
Authors: Katarzyna Skrzypczynska / Kristin Schimert / Heather Stephenson / In Kyoung Mah / David Mortenson / Kelli Boyd / Timothy Hardman / Nikolai Novikov / Elbert Seto / Sabrina Lu / Randy Yen / ...Authors: Katarzyna Skrzypczynska / Kristin Schimert / Heather Stephenson / In Kyoung Mah / David Mortenson / Kelli Boyd / Timothy Hardman / Nikolai Novikov / Elbert Seto / Sabrina Lu / Randy Yen / Brian Lee / Min Wang / Don Kang / Ying Huang / Xinchao Yu / Magdeleine Hung / Sheng Ding / Nathan Thomsen / Nicole Schirle Oakdale /
Abstract: Bispecific T cell engager (TCE) therapies have demonstrated transformative clinical success in the treatment of hematological cancers, but the lack of antigens that are sufficiently selective for ...Bispecific T cell engager (TCE) therapies have demonstrated transformative clinical success in the treatment of hematological cancers, but the lack of antigens that are sufficiently selective for malignant cells has hampered the success of TCEs in the solid-tumor space. To overcome the on-target, off-tumor toxicities that result from the expression of even low levels of tumor-associated antigens in healthy tissues, we sought to identify a TCE target with highly tumor-restricted expression patterns. Here, we characterize cancer-testes antigen Preferentially Expressed Antigen in Melanoma (PRAME) as a highly selective tumor antigen and identify a proteasomal degradation peptide PRAME (PRAME) presented in the context of major histocompatibility complex I (MHCI) as an attractive TCE target. We designed a TCR-mimic (TCRm) antibody screening cascade that prioritizes screening anti-PRAME pMHC binders in off-target T cell dependent cellular cytotoxicity assays in a potent TCE format, rather than relying solely on traditional pMHC binding assays, to determine specificity. Using this screening cascade, we discovered antibodies that selectively bind PRAME pMHC without over-recognition of off-target peptides or MHCI via a TCR-like binding geometry. We further solved the first structure of an anti-PRAME pMHC TCRm antibody in complex with PRAME/HLA-A *02:01 using cryo electron microscopy to confirm the TCRm antibody binds in a TCR-like binding geometry and specifically recognizes the PRAME peptide. By formatting these novel TCRm antibodies into potent TCEs, we demonstrate PRAME pMHC-specific killing of tumor cells, representing a new class of anti-PRAME pMHC biologics.
History
DepositionJul 14, 2025-
Header (metadata) releaseOct 1, 2025-
Map releaseOct 1, 2025-
UpdateApr 29, 2026-
Current statusApr 29, 2026Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_71704.png

Downloads & links

-
Map

FileDownload / File: emd_71704.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.65 Å/pix.
x 400 pix.
= 260. Å		0.65 Å/pix.
x 400 pix.
= 260. Å		0.65 Å/pix.
x 400 pix.
= 260. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.65 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.18
Minimum - Maximum-1.4978926 - 2.1527832
Average (Standard dev.)0.00014852415 (±0.035834737)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 260.0 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #2

Fileemd_71704_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_71704_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : complex of HU38 Fab with PRAME pMHC and anti-Kappa VHH

EntireName: complex of HU38 Fab with PRAME pMHC and anti-Kappa VHH
Components
  • Complex: complex of HU38 Fab with PRAME pMHC and anti-Kappa VHH
    • Protein or peptide: MHC class I antigen
    • Protein or peptide: VHH antibody
    • Protein or peptide: PRAME peptide
    • Protein or peptide: HU-38 Heavy Chain
    • Protein or peptide: Beta-2-microglobulin
    • Protein or peptide: HU-38 Light Chain
  • Ligand: water

-
Supramolecule #1: complex of HU38 Fab with PRAME pMHC and anti-Kappa VHH

SupramoleculeName: complex of HU38 Fab with PRAME pMHC and anti-Kappa VHH
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#6
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: MHC class I antigen

MacromoleculeName: MHC class I antigen / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 34.359895 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: MGSHSMRYFF TSVSRPGRGE PRFIAVGYVD DTQFVRFDSD AASQRMEPRA PWIEQEGPEY WDGETRKVKA HSQTHRVDLG TLRGYYNQS EAGSHTVQRM YGCDVGSDWR FLRGYHQYAY DGKDYIALKE DLRSWTAADM AAQTTKHKWE AAHVAEQLRA Y LEGTCVEW ...String:
MGSHSMRYFF TSVSRPGRGE PRFIAVGYVD DTQFVRFDSD AASQRMEPRA PWIEQEGPEY WDGETRKVKA HSQTHRVDLG TLRGYYNQS EAGSHTVQRM YGCDVGSDWR FLRGYHQYAY DGKDYIALKE DLRSWTAADM AAQTTKHKWE AAHVAEQLRA Y LEGTCVEW LRRYLENGKE TLQRTDAPKT HMTHHAVSDH EATLRCWALS FYPAEITLTW QRDGEDQTQD TELVETRPAG DG TFQKWAA VVVPSGQEQR YTCHVQHEGL PKPLTLRWEP GSGGSGGSAG GGLNDIFEAQ KIEW

UniProtKB: MHC class I antigen

-
Macromolecule #2: VHH antibody

MacromoleculeName: VHH antibody / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Lama glama (llama)
Molecular weightTheoretical: 13.246515 KDa
Recombinant expressionOrganism: Saccharomyces cerevisiae (brewer's yeast)
SequenceString:
QVQLQESGGG LVQPGGSLRL SCAASGRTIS RYAMSWFRQA PGKEREFVAV ARRSGDGAFY ADSVQGRFTV SRDDAKNTVY LQMNSLKPE DTAVYYCAID SDTFYSGSYD YWGQGTQVTV SS

-
Macromolecule #3: PRAME peptide

MacromoleculeName: PRAME peptide / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 994.209 Da
SequenceString:
SLLQHLIGL

-
Macromolecule #4: HU-38 Heavy Chain

MacromoleculeName: HU-38 Heavy Chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 25.680639 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: QVQLQESGPG LVKPSETLSL TCTVSGGSIS TYYWSWIRQP PGKGLEWIGY IYYSGSTNYN PSLKSRVTIS VDTSKNQFSL KLSSVTAAD MAVYYCARIT EIHDAFEIWG QGTMVTVSSA STKGPSVFPL APSSKSTSGG TAALGCLVKD YFPEPVTVSW N SGALTSGV ...String:
QVQLQESGPG LVKPSETLSL TCTVSGGSIS TYYWSWIRQP PGKGLEWIGY IYYSGSTNYN PSLKSRVTIS VDTSKNQFSL KLSSVTAAD MAVYYCARIT EIHDAFEIWG QGTMVTVSSA STKGPSVFPL APSSKSTSGG TAALGCLVKD YFPEPVTVSW N SGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKRVEP KSCHHHHHHH HDYKDDDDK

-
Macromolecule #5: Beta-2-microglobulin

MacromoleculeName: Beta-2-microglobulin / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 11.879356 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
MIQRTPKIQV YSRHPAENGK SNFLNCYVSG FHPSDIEVDL LKNGERIEKV EHSDLSFSKD WSFYLLYYTE FTPTEKDEYA CRVNHVTLS QPKIVKWDRD M

UniProtKB: Beta-2-microglobulin

-
Macromolecule #6: HU-38 Light Chain

MacromoleculeName: HU-38 Light Chain / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 23.287822 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DIHMTQSPSS VSASVGDRVT ITCRASQGIS SWLAWYQQKP GKAPKLLIYA ASSLQSGVPS RFSGSESGTD FTLTISSLQP EDFATYYCQ QANSFPFTFG PGTKVDIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS ...String:
DIHMTQSPSS VSASVGDRVT ITCRASQGIS SWLAWYQQKP GKAPKLLIYA ASSLQSGVPS RFSGSESGTD FTLTISSLQP EDFATYYCQ QANSFPFTFG PGTKVDIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC

-
Macromolecule #7: water

MacromoleculeName: water / type: ligand / ID: 7 / Number of copies: 191 / Formula: HOH
Molecular weightTheoretical: 18.015 Da
Chemical component information

ChemComp-HOH:
WATER

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.4
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 10 K / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE / Details: ab initio
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.72 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 553793
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
FSC plot (resolution estimation)

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more