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- EMDB-61724: Cryo-EM structure of BTN2A1 in complex with antagonist antibody TH002 -

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Basic information

Entry
Database: EMDB / ID: EMD-61724
TitleCryo-EM structure of BTN2A1 in complex with antagonist antibody TH002
Map data
Sample
  • Complex: full-length BTN2A1 in complex with its antagonist antibody TH002
    • Protein or peptide: Butyrophilin subfamily 2 member A1
    • Protein or peptide: BTN2A1 antagonist antibody TH002-Fab heavy chain
    • Protein or peptide: BTN2A1 antagonist antibody TH002-Fab light chain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
Keywordsreceptor / butyrophilin / antagonist / antibody / IMMUNE SYSTEM
Function / homology
Function and homology information


Butyrophilin (BTN) family interactions / regulation of cytokine production / lipid metabolic process / T cell receptor signaling pathway / external side of plasma membrane / signaling receptor binding / plasma membrane
Similarity search - Function
Butyrophilin subfamily 1/2, SPRY/PRY domain / : / : / Butyrophilin subfamily 3 member A2-like, Ig-C domain / SPRY-associated domain / SPRY-associated / PRY / Butyrophylin-like, SPRY domain / SPRY domain / B30.2/SPRY domain ...Butyrophilin subfamily 1/2, SPRY/PRY domain / : / : / Butyrophilin subfamily 3 member A2-like, Ig-C domain / SPRY-associated domain / SPRY-associated / PRY / Butyrophylin-like, SPRY domain / SPRY domain / B30.2/SPRY domain / B30.2/SPRY domain profile. / B30.2/SPRY domain superfamily / Domain in SPla and the RYanodine Receptor. / SPRY domain / Immunoglobulin V-Type / Immunoglobulin V-set domain / Immunoglobulin V-set domain / Immunoglobulin subtype / Immunoglobulin / Concanavalin A-like lectin/glucanase domain superfamily / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold
Similarity search - Domain/homology
Butyrophilin subfamily 2 member A1
Similarity search - Component
Biological speciesHomo sapiens (human) / Mus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.34 Å
AuthorsZhang M / Wang YQ / Xiao JY
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)32325018 China
CitationJournal: Immunity / Year: 2025
Title: Structures of butyrophilin multimers reveal a plier-like mechanism for Vγ9Vδ2 T cell receptor activation.
Authors: Mai Zhang / Yiqing Wang / Ningning Cai / Yingying Qu / Xianqiang Ma / Jing Xue / Xiaorui Chen / Xueguang Zhang / Junyu Xiao / Yonghui Zhang /
Abstract: Vγ9Vδ2 T cells, the major circulating human γδ T cell subset, respond to infections and tumors by recognizing phosphoantigens (pAgs) via transmembrane butyrophilins (BTN3A1, BTN3A2, and BTN2A1). ...Vγ9Vδ2 T cells, the major circulating human γδ T cell subset, respond to infections and tumors by recognizing phosphoantigens (pAgs) via transmembrane butyrophilins (BTN3A1, BTN3A2, and BTN2A1). Here, using cryoelectron microscopy, we resolved the structures of BTN multimers bound to the microbial pAg HMBPP alone and in complex with the T cell receptor (TCR). These structures reveal that BTN3A1 and BTN2A1 cooperate to sense pAgs through their intracellular B30.2 domains, whereas BTN3A2 and BTN2A1 interact extracellularly. TCR engagement triggers its conformational changes, allowing BTN2A1 to bind the Vγ9 chain laterally and BTN3A2 to interact apically with the Vδ2 chain's germline-encoded regions and CDR3 motif, as well as the Vγ9 CDR3. Our study uncovers a "plier-like gripping" mechanism, where BTN multimers bridge the TCR surface to drive activation. These findings establish a structural foundation for γδ T cell-targeted immunotherapies distinct from αβ T cell strategies reliant on major-histocompatibility-complex-mediated antigen presentation.
History
DepositionSep 27, 2024-
Header (metadata) releaseJun 18, 2025-
Map releaseJun 18, 2025-
UpdateJun 25, 2025-
Current statusJun 25, 2025Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_61724.png

Downloads & links

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Map

FileDownload / File: emd_61724.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.)
0.95 Å/pix.
x 400 pix.
= 380. Å		0.95 Å/pix.
x 400 pix.
= 380. Å		0.95 Å/pix.
x 400 pix.
= 380. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.95 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 4.0
Minimum - Maximum-0.13243014 - 17.000216000000002
Average (Standard dev.)-0.033089608 (±0.27854058)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 380.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Additional map: B-factor sharpened

Fileemd_61724_additional_1.map
AnnotationB-factor sharpened
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_61724_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_61724_half_map_2.map
Projections & Slices
AxesZYX

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Histogram

Histogram (log scale)

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Sample components

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Entire : full-length BTN2A1 in complex with its antagonist antibody TH002

EntireName: full-length BTN2A1 in complex with its antagonist antibody TH002
Components
  • Complex: full-length BTN2A1 in complex with its antagonist antibody TH002
    • Protein or peptide: Butyrophilin subfamily 2 member A1
    • Protein or peptide: BTN2A1 antagonist antibody TH002-Fab heavy chain
    • Protein or peptide: BTN2A1 antagonist antibody TH002-Fab light chain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: full-length BTN2A1 in complex with its antagonist antibody TH002

SupramoleculeName: full-length BTN2A1 in complex with its antagonist antibody TH002
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Butyrophilin subfamily 2 member A1

MacromoleculeName: Butyrophilin subfamily 2 member A1 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 60.015312 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: QFIVVGPTDP ILATVGENTT LRCHLSPEKN AEDMEVRWFR SQFSPAVFVY KGGRERTEEQ MEEYRGRTTF VSKDISRGSV ALVIHNITA QENGTYRCYF QEGRSYDEAI LHLVVAGLGS KPLISMRGHE DGGIRLECIS RGWYPKPLTV WRDPYGGVAP A LKEVSMPD ...String:
QFIVVGPTDP ILATVGENTT LRCHLSPEKN AEDMEVRWFR SQFSPAVFVY KGGRERTEEQ MEEYRGRTTF VSKDISRGSV ALVIHNITA QENGTYRCYF QEGRSYDEAI LHLVVAGLGS KPLISMRGHE DGGIRLECIS RGWYPKPLTV WRDPYGGVAP A LKEVSMPD ADGLFMVTTA VIIRDKSVRN MSCSINNTLL GQKKESVIFI PESFMPSVSP CAVALPIIVV ILMIPIAVCI YW INKLQKE KKILSGEKEF ERETREIALK ELEKERVQKE EELQVKEKLQ EELRWRRTFL HAVDVVLDPD TAHPDLFLSE DRR SVRRCP FRHLGESVPD NPERFDSQPC VLGRESFASG KHYWEVEVEN VIEWTVGVCR DSVERKGEVL LIPQNGFWTL EMHK GQYRA VSSPDRILPL KESLCRVGVF LDYEAGDVSF YNMRDRSHIY TCPRSAFSVP VRPFFRLGCE DSPIFICPAL TGANG VTVP EEGLTLHRVG THQSLGGGGS WSHPQFEKGG GSGGGSGGSA WSHPQFEK

UniProtKB: Butyrophilin subfamily 2 member A1

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Macromolecule #2: BTN2A1 antagonist antibody TH002-Fab heavy chain

MacromoleculeName: BTN2A1 antagonist antibody TH002-Fab heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 24.961285 KDa
Recombinant expressionOrganism: Mus musculus (house mouse)
SequenceString: EVKLLESGGG LVQPGGSLKL SCAASGFDFS RYWMSWVRQA PGKGLEWIGE INPGSITINY TPSLKDKFII SRDNAKNTLY LQMSKVSSE DTALYYCARQ RKWFRRDAMD YWGQGTSVTV SSAKTTAPSV YPLAPVCGDT TGSSVTLGCL VKGYFPEPVT L TWNSGSLS ...String:
EVKLLESGGG LVQPGGSLKL SCAASGFDFS RYWMSWVRQA PGKGLEWIGE INPGSITINY TPSLKDKFII SRDNAKNTLY LQMSKVSSE DTALYYCARQ RKWFRRDAMD YWGQGTSVTV SSAKTTAPSV YPLAPVCGDT TGSSVTLGCL VKGYFPEPVT L TWNSGSLS SGVHTFPAVL QSDLYTLSSS VTVTSSTWPS QSITCNVAHP ASSTKVDKKI EPRGPTIKPC PPC

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Macromolecule #3: BTN2A1 antagonist antibody TH002-Fab light chain

MacromoleculeName: BTN2A1 antagonist antibody TH002-Fab light chain / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 23.813033 KDa
Recombinant expressionOrganism: Mus musculus (house mouse)
SequenceString: DIVLTQSPAS LAVSLGQRAT VSCKASHSVD YDGDSYVNWY QQKPGQPPKL LISAASNLES GIPARFSGSG SGTDFTLNIH PVEEEDAAT YYCQQSYGDP WTFGGGTKLE IKRADAAPTV SIFPPSSEQL TSGGASVVCF LNNFYPKDIN VKWKIDGSER Q NGVLNSWT ...String:
DIVLTQSPAS LAVSLGQRAT VSCKASHSVD YDGDSYVNWY QQKPGQPPKL LISAASNLES GIPARFSGSG SGTDFTLNIH PVEEEDAAT YYCQQSYGDP WTFGGGTKLE IKRADAAPTV SIFPPSSEQL TSGGASVVCF LNNFYPKDIN VKWKIDGSER Q NGVLNSWT DQDSKDSTYS MSSTLTLTKD EYERHNSYTC EATHKTSTSP IVKSFNRNEC

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Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 7 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

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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: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.7 µm / Nominal defocus min: 1.3 µm
Experimental equipment
Model: Titan Krios / 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: 3.34 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 247369
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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