Crystal structure of the complex between programmed death-1 (PD-1) and its ligand PD-L2

• DOI: 10.1073/pnas.0804453105
• Publication Date: 2008-07-19T00:54:33Z
• Authors: Eszter Lázár-Molnár; Qingrong Yan; Erhu Cao; Udupi Ramagopal; Stanley G. Nathenson; Steven C. Almo
• Keywords: Immunological synapse

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 complex formed by complete ectodomains murine PD-1 and PD-L2 revealed 1:1 receptor:ligand stoichiometry displayed binding interface overall molecular organization distinct from observed in CTLA-4/B7 inhibitory complexes. Furthermore, our also provides insights into association between highlights differences interfaces ligands (PD-Ls) Mutagenesis studies confirmed details proposed PD-1/PD-L allowed for design mutant receptor enhanced affinity. These define spatial organizational constraints control localization signaling complexes within immunological synapse provide basis manipulating pathways immunotherapy.