The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.
Structure and Interactions of the Human Programmed Cell Death 1 Receptor
Open accessAbstract
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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Cites
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Metadata
- Authors
- Cheng, X., Veverka, V., Radhakrishnan, A., Waters, L. C., Muskett, F. W., Morgan, S. H., Huo, J., Yu, C., Evans, E. J., Leslie, A. J., Griffiths, M., Stubberfield, C., Griffin, R., Henry, A. J., Jansson, A., Ladbury, J. E., Ikemizu, S., Carr, M. D., & Davis, S. J.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2013-04
- Volume
- 288
- Issue
- 17
- Pages
- 11771-11785
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2090031443
- Cited by
- 323
- References
- 66
- FWCI
- 5.85
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Cheng, X., Veverka, V., Radhakrishnan, A., Waters, L. C., Muskett, F. W., Morgan, S. H., Huo, J., Yu, C., Evans, E. J., Leslie, A. J., Griffiths, M., Stubberfield, C., Griffin, R., Henry, A. J., Jansson, A., Ladbury, J. E., Ikemizu, S., Carr, M. D., & Davis, S. J. (2013). Structure and Interactions of the Human Programmed Cell Death 1 Receptor. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m112.448126
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
