Structure of the Complex of Human Programmed Death 1, PD-1, and Its Ligand PD-L1

Structure. 2015 Dec 1;23(12):2341-2348. doi: 10.1016/j.str.2015.09.010. Epub 2015 Oct 22.


Targeting the PD-1/PD-L1 immunologic checkpoint with monoclonal antibodies has recently provided breakthrough progress in the treatment of melanoma, non-small cell lung cancer, and other types of cancer. Small-molecule drugs interfering with this pathway are highly awaited, but their development is hindered by insufficient structural information. This study reveals the molecular details of the human PD-1/PD-L1 interaction based on an X-ray structure of the complex. First, it is shown that the ligand binding to human PD-1 is associated with significant plasticity within the receptor. Second, a detailed molecular map of the interaction surface is provided, allowing definition of the regions within both interacting partners that may likely be targeted by small molecules.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • B7-H1 Antigen / chemistry*
  • B7-H1 Antigen / metabolism
  • Binding Sites
  • Humans
  • Molecular Sequence Data
  • Programmed Cell Death 1 Receptor / chemistry*
  • Programmed Cell Death 1 Receptor / metabolism
  • Protein Binding


  • B7-H1 Antigen
  • Programmed Cell Death 1 Receptor

Associated data

  • PDB/4ZQK
  • PDB/5C3T