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- PDB-9w43: Structure of the complex of human PD-1 and a PD-1-directed antibody -

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Basic information

Entry
Database: PDB / ID: 9w43
TitleStructure of the complex of human PD-1 and a PD-1-directed antibody
Components
  • Heavy chain of 1C4 Fab fragment
  • Light chain of 1C4 Fab fragment
  • Programmed cell death protein 1
KeywordsIMMUNE SYSTEM / PD-1 / PD-1-directed antibody / antigen-antibody complex
Function / homology
Function and homology information


negative regulation of immune response / negative regulation of T cell mediated immune response to tumor cell / negative regulation of T cell activation / humoral immune response / Co-inhibition by PD-1 / regulation of immune response / negative regulation of T cell receptor signaling pathway / PD-L1(CD274) glycosylation and translocation to plasma membrane / negative regulation of inflammatory response / transmembrane signaling receptor activity ...negative regulation of immune response / negative regulation of T cell mediated immune response to tumor cell / negative regulation of T cell activation / humoral immune response / Co-inhibition by PD-1 / regulation of immune response / negative regulation of T cell receptor signaling pathway / PD-L1(CD274) glycosylation and translocation to plasma membrane / negative regulation of inflammatory response / transmembrane signaling receptor activity / signaling receptor activity / Potential therapeutics for SARS / adaptive immune response / external side of plasma membrane / apoptotic process / plasma membrane
Similarity search - Function
Programmed cell death protein 1 / Immunoglobulin V-Type / Immunoglobulin V-set domain / Immunoglobulin V-set domain / Immunoglobulin subtype / Immunoglobulin / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold
Similarity search - Domain/homology
Programmed cell death protein 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.96 Å
AuthorsJiang, W.B. / Xu, J.L.
Funding support1items
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, 2025Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Jul 1, 2026Provider: repository / Type: Initial release
Revision 1.0Jul 1, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Jul 1, 2026Data content type: FSC / Data content type: FSC / Provider: repository / Type: Initial release
Revision 1.0Jul 1, 2026Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jul 1, 2026Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jul 1, 2026Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Jul 1, 2026Data content type: Mask / Part number: 1 / Data content type: Mask / Provider: repository / Type: Initial release
Revision 1.0Jul 1, 2026Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Heavy chain of 1C4 Fab fragment
B: Light chain of 1C4 Fab fragment
C: Programmed cell death protein 1


Theoretical massNumber of molelcules
Total (without water)58,9403
Polymers58,9403
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

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Components

#1: Antibody Heavy chain of 1C4 Fab fragment


Mass: 22857.650 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Cricetulus griseus (Chinese hamster)
#2: Antibody Light chain of 1C4 Fab fragment


Mass: 23194.764 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Cricetulus griseus (Chinese hamster)
#3: Protein Programmed cell death protein 1 / Protein PD-1 / hPD-1


Mass: 12887.396 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PDCD1, PD1 / Production host: Homo sapiens (human) / References: UniProt: Q15116
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: PD1-fab complex / Type: COMPLEX / Entity ID: all / Source: MULTIPLE SOURCES
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Cricetulus griseus (Chinese hamster)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2400 nm / Nominal defocus min: 1000 nm
Image recordingElectron dose: 59 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

EM software
IDNameCategory
1cryoSPARCparticle selection
13cryoSPARC3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 2.96 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 179370 / Symmetry type: POINT

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