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- EMDB-65617: Structure of the complex of human PD-1 and a PD-1-directed antibody -

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Basic information

Entry
Database: EMDB / ID: EMD-65617
TitleStructure of the complex of human PD-1 and a PD-1-directed antibody
Map data
Sample
  • Complex: PD1-fab complex
    • Protein or peptide: Heavy chain of 1C4 Fab fragment
    • Protein or peptide: Light chain of 1C4 Fab fragment
    • Protein or peptide: Programmed cell death protein 1
KeywordsPD-1 / PD-1-directed antibody / antigen-antibody complex / IMMUNE SYSTEM
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.96 Å
AuthorsJiang WB / Xu JL
Funding support1 items
OrganizationGrant numberCountry
Not funded
CitationJournal: MAbs / Year: 2026
Title: Dual agonism and selective T-cell depletion activity of a PD-1-directed antibody for treating autoimmune diseases.
Authors: Wenbo Jiang / Lingyun Li / Weili Xue / Xuzhi He / Xuebin Chu / Lei Song / Xue Li / Ranran Zhao / Xinghang Yuan / Xiaoliang Jin / Lishi Fan / Tian Sun / Aisi Zhu / Ling Zhou / Fei Gu / Qian ...Authors: Wenbo Jiang / Lingyun Li / Weili Xue / Xuzhi He / Xuebin Chu / Lei Song / Xue Li / Ranran Zhao / Xinghang Yuan / Xiaoliang Jin / Lishi Fan / Tian Sun / Aisi Zhu / Ling Zhou / Fei Gu / Qian Xu / Guangli Ma / Siqin Wang / Lei Jin / John L Xu /
Abstract: Precise inhibition of autoreactivity without concomitant induction of general immunosuppression is an overarching goal that remains elusive for the treatment of autoimmune diseases. PD-1 is ...Precise inhibition of autoreactivity without concomitant induction of general immunosuppression is an overarching goal that remains elusive for the treatment of autoimmune diseases. PD-1 is preferentially expressed on activated T cells that drive autoimmunity. These PD-1 T cells could serve as a target for therapeutic intervention. Here, we report the discovery of a unique PD-1 agonist antibody, GenSci120, that exhibited potent and selective T-cell inhibition in vitro and T-cell depletion activity both in vitro and in vivo. Target engagement by GenSci120 directly promoted SHP2 recruitment into the PD-1 signaling pathway but also enhanced the binding of PD-1 to its natural ligands and augmented PD-L1-induced PD-1 signaling. Moreover, GenSci120 exhibited robust efficacy in several animal models of human autoimmune disease. Thus, GenSci120, by selectively depleting PD-1 T cells and by directly (via PD-1 binding and SHP2 recruitment) or indirectly (via enhancing PD-1 and ligand interaction) stimulating PD-1 signaling, has the capability to restore immune balance in autoimmunity. In a first-in-human study in healthy adults (NCT06827457), GenSci120 demonstrated favorable safety/tolerability and pharmacokinetic profiles as well as robust pharmacodynamic effect. Together, these findings suggest the potential of GenSci120 as an innovative precision medicine for treating autoimmune diseases and support further evaluation of this investigational new drug in future clinical trials.
History
DepositionJul 30, 2025-
Header (metadata) releaseJul 1, 2026-
Map releaseJul 1, 2026-
UpdateJul 1, 2026-
Current statusJul 1, 2026Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_65617.png

Downloads & links

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Map

FileDownload / File: emd_65617.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.)
0.82 Å/pix.
x 300 pix.
= 245.7 Å		0.82 Å/pix.
x 300 pix.
= 245.7 Å		0.82 Å/pix.
x 300 pix.
= 245.7 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.819 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.323
Minimum - Maximum-1.2929322 - 1.9314039
Average (Standard dev.)-0.00007384421 (±0.042825017)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions300300300
Spacing300300300
CellA=B=C: 245.7 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_65617_msk_1.map
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AxesZYX

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Half map: #2

Fileemd_65617_half_map_1.map
Projections & Slices
AxesZYX

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Histogram

Histogram (log scale)

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Half map: #1

Fileemd_65617_half_map_2.map
Projections & Slices
AxesZYX

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Sample components

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Entire : PD1-fab complex

EntireName: PD1-fab complex
Components
  • Complex: PD1-fab complex
    • Protein or peptide: Heavy chain of 1C4 Fab fragment
    • Protein or peptide: Light chain of 1C4 Fab fragment
    • Protein or peptide: Programmed cell death protein 1

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Supramolecule #1: PD1-fab complex

SupramoleculeName: PD1-fab complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Heavy chain of 1C4 Fab fragment

MacromoleculeName: Heavy chain of 1C4 Fab fragment / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 22.85765 KDa
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
SequenceString: QVQLVQSGAE VKKPGASVKV SCKASGYTFT SYWITWIRQA PGQGLEWIGR IAPGSGSIYY DEMFKDRVTM TVDPSTSTAY IELSSLRSE DTAVYYCARL GNYGWTMDYW GQGTTVTVSS ASTKGPSVFP LAPSGTAALG CLVKDYFPEP VTVSWNSGAL T SGVHTFPA ...String:
QVQLVQSGAE VKKPGASVKV SCKASGYTFT SYWITWIRQA PGQGLEWIGR IAPGSGSIYY DEMFKDRVTM TVDPSTSTAY IELSSLRSE DTAVYYCARL GNYGWTMDYW GQGTTVTVSS ASTKGPSVFP LAPSGTAALG CLVKDYFPEP VTVSWNSGAL T SGVHTFPA VLQSSGLYSL SSVVTVPSSS LGTQTYICNV NHKPSNTKVD KKVEP

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Macromolecule #2: Light chain of 1C4 Fab fragment

MacromoleculeName: Light chain of 1C4 Fab fragment / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23.194764 KDa
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
SequenceString: DIVMTQSPKS LAVSLGERAT INCKASQSVT NNVAWYQQKP GQPPKLLIYY VSNRYTGVPD RFSGSGYGTD FTLTISSLQA EDVAVYFCQ QDYSSWTFGG GTKVEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ E SVTEQDSK ...String:
DIVMTQSPKS LAVSLGERAT INCKASQSVT NNVAWYQQKP GQPPKLLIYY VSNRYTGVPD RFSGSGYGTD FTLTISSLQA EDVAVYFCQ QDYSSWTFGG GTKVEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ E SVTEQDSK DSTYSLSSTL TLSKADYEKH KVYACEVTHQ GLSSPVTKSF NRG

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Macromolecule #3: Programmed cell death protein 1

MacromoleculeName: Programmed cell death protein 1 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 12.887396 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
NPPTFSPALL VVTEGDNATF TCSFSNTSES FVLNWYRMSP SNQTDKLAAF PEDRSQPGQD CRFRVTQLPN GRDFHMSVVR ARRNDSGTY LCGAISLAPK AQIKESLRAE LRVTER

UniProtKB: Programmed cell death protein 1

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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

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 59.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.4 µm / Nominal defocus min: 1.0 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: OTHER / Details: CryoSPARC Ab-initio reconstruction
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.96 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 179370
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION
FSC plot (resolution estimation)

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