Structural and functional analysis of the costimulatory receptor programmed death-1.
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.
Zhang
Xuewu
X
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461 USA.
Schwartz
Jean-Claude D
JC
Guo
Xiaoling
X
Bhatia
Sumeena
S
Cao
Erhu
E
Lorenz
Michael
M
Cammer
Michael
M
Chen
Lieping
L
Zhang
Zhong-Yin
ZY
Edidin
Michael A
MA
Nathenson
Stanley G
SG
Almo
Steven C
SC
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D060890:B7-H1 Antigen; D001798:Blood Proteins; D060908:CTLA-4 Antigen; D007135:Immunoglobulin Variable Region / Q000737:chemistry; D008024:Ligands; D008562:Membrane Glycoproteins; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010455:Peptides; D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D001798:Blood Proteins; D060908:CTLA-4 Antigen; C498919:Cd274 protein, mouse; C556707:Ctla4 protein, mouse; D007135:Immunoglobulin Variable Region; D008024:Ligands; D008562:Membrane Glycoproteins; C491383:Pdcd1 protein, mouse; D010455:Peptides; D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic