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

Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10483-8. doi: 10.1073/pnas.0804453105. Epub 2008 Jul 18.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Surface / metabolism*
  • Apoptosis Regulatory Proteins / metabolism*
  • Crystallography, X-Ray / methods*
  • Escherichia coli / metabolism
  • Ligands
  • Lymphocyte Activation
  • Mice
  • Molecular Sequence Data
  • Mutation
  • Peptides / metabolism*
  • Programmed Cell Death 1 Ligand 2 Protein
  • Programmed Cell Death 1 Receptor
  • Protein Conformation
  • Protein Structure, Secondary
  • Sequence Homology, Amino Acid
  • T-Lymphocytes / cytology


  • Antigens, Surface
  • Apoptosis Regulatory Proteins
  • Ligands
  • Pdcd1 protein, mouse
  • Pdcd1lg2 protein, mouse
  • Peptides
  • Programmed Cell Death 1 Ligand 2 Protein
  • Programmed Cell Death 1 Receptor

Associated data

  • PDB/3BOV
  • PDB/3BP5