| http://purl.uniprot.org/citations/23417675 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23417675 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23417675 | http://www.w3.org/2000/01/rdf-schema#comment | "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."xsd:string |
| http://purl.uniprot.org/citations/23417675 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m112.448126"xsd:string |
| http://purl.uniprot.org/citations/23417675 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m112.448126"xsd:string |
| http://purl.uniprot.org/citations/23417675 | http://purl.uniprot.org/core/author | "Cheng X."xsd:string |
| http://purl.uniprot.org/citations/23417675 | http://purl.uniprot.org/core/author | "Cheng X."xsd:string |
| http://purl.uniprot.org/citations/23417675 | http://purl.uniprot.org/core/author | "Yu C."xsd:string |
| http://purl.uniprot.org/citations/23417675 | http://purl.uniprot.org/core/author | "Yu C."xsd:string |
| http://purl.uniprot.org/citations/23417675 | http://purl.uniprot.org/core/author | "Ikemizu S."xsd:string |
| http://purl.uniprot.org/citations/23417675 | http://purl.uniprot.org/core/author | "Ikemizu S."xsd:string |
| http://purl.uniprot.org/citations/23417675 | http://purl.uniprot.org/core/author | "Radhakrishnan A."xsd:string |
| http://purl.uniprot.org/citations/23417675 | http://purl.uniprot.org/core/author | "Radhakrishnan A."xsd:string |
| http://purl.uniprot.org/citations/23417675 | http://purl.uniprot.org/core/author | "Veverka V."xsd:string |
| http://purl.uniprot.org/citations/23417675 | http://purl.uniprot.org/core/author | "Veverka V."xsd:string |
| http://purl.uniprot.org/citations/23417675 | http://purl.uniprot.org/core/author | "Davis S.J."xsd:string |
| http://purl.uniprot.org/citations/23417675 | http://purl.uniprot.org/core/author | "Davis S.J."xsd:string |
| http://purl.uniprot.org/citations/23417675 | http://purl.uniprot.org/core/author | "Muskett F.W."xsd:string |
| http://purl.uniprot.org/citations/23417675 | http://purl.uniprot.org/core/author | "Muskett F.W."xsd:string |
| http://purl.uniprot.org/citations/23417675 | http://purl.uniprot.org/core/author | "Griffiths M."xsd:string |
| http://purl.uniprot.org/citations/23417675 | http://purl.uniprot.org/core/author | "Griffiths M."xsd:string |
| http://purl.uniprot.org/citations/23417675 | http://purl.uniprot.org/core/author | "Jansson A."xsd:string |
| http://purl.uniprot.org/citations/23417675 | http://purl.uniprot.org/core/author | "Jansson A."xsd:string |
| http://purl.uniprot.org/citations/23417675 | http://purl.uniprot.org/core/author | "Carr M.D."xsd:string |
| http://purl.uniprot.org/citations/23417675 | http://purl.uniprot.org/core/author | "Carr M.D."xsd:string |