Structural and functional analysis of the costimulatory receptor programmed death-1

Immunity. 2004 Mar;20(3):337-47. doi: 10.1016/s1074-7613(04)00051-2.


PD-1, a member of the CD28/CTLA-4/ICOS costimulatory receptor family, delivers negative signals that have profound effects on T and B cell immunity. The 2.0 A crystal structure of the extracellular domain of murine PD-1 reveals an Ig V-type topology with overall similarity to the CTLA-4 monomer; however, there are notable differences in regions relevant to function. Our structural and biophysical data show that PD-1 is monomeric both in solution as well as on cell surface, in contrast to CTLA-4 and other family members that are all disulfide-linked homodimers. Furthermore, our structure-based mutagenesis studies identify the ligand binding surface of PD-1, which displays significant differences compared to those present in the other members of the family.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, CD
  • Antigens, Differentiation / chemistry*
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / metabolism
  • B7-1 Antigen / metabolism
  • B7-H1 Antigen
  • Blood Proteins*
  • CTLA-4 Antigen
  • Immunoglobulin Variable Region / chemistry
  • Ligands
  • Membrane Glycoproteins
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Peptides*
  • Programmed Cell Death 1 Receptor
  • Receptors, Immunologic / chemistry*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Sequence Alignment


  • Antigens, CD
  • Antigens, Differentiation
  • B7-1 Antigen
  • B7-H1 Antigen
  • Blood Proteins
  • CTLA-4 Antigen
  • Cd274 protein, mouse
  • Ctla4 protein, mouse
  • Immunoglobulin Variable Region
  • Ligands
  • Membrane Glycoproteins
  • Pdcd1 protein, mouse
  • Peptides
  • Programmed Cell Death 1 Receptor
  • Receptors, Immunologic

Associated data

  • PDB/1NPU