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Yorodumi- PDB-9w43: Structure of the complex of human PD-1 and a PD-1-directed antibody -
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Open data
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Basic information
| Entry | Database: PDB / ID: 9w43 | |||||||||||||||||||||||||||
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| Title | Structure of the complex of human PD-1 and a PD-1-directed antibody | |||||||||||||||||||||||||||
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Keywords | IMMUNE SYSTEM / PD-1 / PD-1-directed antibody / antigen-antibody complex | |||||||||||||||||||||||||||
| Function / homology | Function and homology informationnegative 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 | |||||||||||||||||||||||||||
| Biological species | Homo sapiens (human) | |||||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.96 Å | |||||||||||||||||||||||||||
Authors | Jiang, W.B. / Xu, J.L. | |||||||||||||||||||||||||||
| Funding support | 1items
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Citation | Journal: MAbs / Year: 2026Title: 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 |
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 9w43.cif.gz | 178.9 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb9w43.ent.gz | 144.8 KB | Display | PDB format |
| PDBx/mmJSON format | 9w43.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/w4/9w43 ftp://data.pdbj.org/pub/pdb/validation_reports/w4/9w43 | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 65617MC M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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Components
| #1: Antibody | Mass: 22857.650 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: ![]() |
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| #2: Antibody | Mass: 23194.764 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: ![]() |
| #3: Protein | 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 modification | Y |
-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
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| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
| Component | Name: PD1-fab complex / Type: COMPLEX / Entity ID: all / Source: MULTIPLE SOURCES |
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| Source (natural) | Organism: Homo sapiens (human) |
| Source (recombinant) | Organism: ![]() |
| Buffer solution | pH: 7.5 |
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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| Microscopy | Model: TFS KRIOS |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2400 nm / Nominal defocus min: 1000 nm |
| Image recording | Electron dose: 59 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
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| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||
| 3D reconstruction | Resolution: 2.96 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 179370 / Symmetry type: POINT |
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Homo sapiens (human)
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FIELD EMISSION GUN