ArticleThe Journal of biological chemistry2013
Structure and interactions of the human programmed cell death 1 receptor.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 188 papers, 2 of them syntheses that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
188 citing papers in PubMed, 2 syntheses or guidelines pooled it, 324 citations in OpenAlex.
- Checkpoint inhibitor immunotherapy for glioblastoma: current progress, challenges and future outlook.Expert review of clinical pharmacology · 2020Pooled it
- Chemotherapy and immunotherapy for recurrent and metastatic head and neck cancer: a systematic review.Medical oncology (Northwood, London, England) · 2018Pooled it
- Unveiling the role of circulating monocyte-macrophage polarization state and PD-L1/PD-L2 expression in newly diagnosed pediatric ITP.Blood research · 2026Article
- Humanized Anti-PD-1 Antibodies Generated Using The Conditional Kernel-Elastic Autoencoder.bioRxiv : the preprint server for biology · 2026Article
- Computational screening of Viola odorata cyclotides identifies Phyb C as potential PD-1 inhibitor for cancer immunotherapy.Molecular diversity · 2026Article
- PD-1⁺ CD8⁺ T cells: roles of PD-1 beyond an exhaustion marker.Seminars in immunopathology · 2026Review
- Peptide design through binding interface mimicry with PepMimic.Nature biomedical engineering · 2026Article
- Understanding the Therapeutic Potential of PD-1 Agonism in Inflammatory and Autoimmune Disorders.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Distinctive features of the tumor and immune microenvironment in glioblastoma.NPJ precision oncology · 2026Article
- Structure-Function Insights into Immune Receptors Drive Innovation in CAR-T Cell Therapy.Current issues in molecular biology · 2026Review
- Efficient Method for High-Throughput Screening of Compound Libraries Targeting Human PD-L1.ACS omega · 2026Article
- Involvement of the PD-1 pathway in the modulation of immune responses during allergic diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Mechanical force regulates the inhibitory function of PD-1.EMBO reports · 2026Article
- The co-delivery of Programmed Death 1 ligands enhances and prolongs rAAV-mediated gene expression in pre-immunized mice.Gene therapy · 2026Article
- Modelling Immune Dynamics in Locally Advanced MSI-H/dMMR Colorectal Cancer with Neoadjuvant Pembrolizumab Treatment: From Differential Equations to an Agent-Based Framework.Bulletin of mathematical biology · 2026Article
- Engineering strategies and binding mechanisms of therapeutic anti-PD-1 antibodies approved by regulatory agencies globally.Frontiers in immunology · 2026Review
- Breaking Barriers: Immune Checkpoint Inhibitors in Breast Cancer.Pharmaceutics · 2025Review
- Directed evolution-driven reprogramming of PD-L1 for compact and tunable checkpoint modulation.Journal of biological engineering · 2025Article
- Ligand-receptor interactions of V-domain Ig-containing suppressor of T cell activation and programmed death-1 suppress the anticancer activities of T cells.Immuno-oncology technology · 2025Article
- Article
128 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 5 institutions in 5 countries.
Funding
Abstract
PD-1, a receptor expressed by T cells, B cells, and monocytes, is a potent regulator of immune responses and a promising therapeutic target. The structure and interactions of human PD-1 are, however, incompletely characterized. We present the solution nuclear magnetic resonance (NMR)-based structure of the human PD-1 extracellular region and detailed analyses of its interactions with its ligands, PD-L1 and PD-L2. PD-1 has typical immunoglobulin superfamily topology but differs at the edge of the GFCC' sheet, which is flexible and completely lacks a C" strand. Changes in PD-1 backbone NMR signals induced by ligand binding suggest that, whereas binding is centered on the GFCC' sheet, PD-1 is engaged by its two ligands differently and in ways incompletely explained by crystal structures of mouse PD-1 · ligand complexes. The affinities of these interactions and that of PD-L1 with the costimulatory protein B7-1, measured using surface plasmon resonance, are significantly weaker than expected. The 3-4-fold greater affinity of PD-L2 versus PD-L1 for human PD-1 is principally due to the 3-fold smaller dissociation rate for PD-L2 binding. Isothermal titration calorimetry revealed that the PD-1/PD-L1 interaction is entropically driven, whereas PD-1/PD-L2 binding has a large enthalpic component. Mathematical simulations based on the biophysical data and quantitative expression data suggest an unexpectedly limited contribution of PD-L2 to PD-1 ligation during interactions of activated T cells with antigen-presenting cells. These findings provide a rigorous structural and biophysical framework for interpreting the important functions of PD-1 and reveal that potent inhibitory signaling can be initiated by weakly interacting receptors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.