3bp5

Publication Abstract from PubMed

Programmed death-1 (PD-1) is a member of the CD28/B7 superfamily that delivers negative signals upon interaction with its two ligands, PD-L1 or PD-L2. The high-resolution crystal structure of the complex formed by the complete ectodomains of murine PD-1 and PD-L2 revealed a 1:1 receptor:ligand stoichiometry and displayed a binding interface and overall molecular organization distinct from that observed in the CTLA-4/B7 inhibitory complexes. Furthermore, our structure also provides insights into the association between PD-1 and PD-L1 and highlights differences in the interfaces formed by the two PD-1 ligands (PD-Ls) Mutagenesis studies confirmed the details of the proposed PD-1/PD-L binding interfaces and allowed for the design of a mutant PD-1 receptor with enhanced affinity. These studies define spatial and organizational constraints that control the localization and signaling of PD-1/PD-L complexes within the immunological synapse and provide a basis for manipulating the PD-1 pathways for immunotherapy.

Crystal structure of the complex between programmed death-1 (PD-1) and its ligand PD-L2.,Lazar-Molnar E, Yan Q, Cao E, Ramagopal U, Nathenson SG, Almo SC Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10483-8. Epub 2008 Jul 18. PMID:18641123^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.