TY - JOUR
T1 - Structural and functional analysis of the costimulatory receptor programmed death-1
AU - Zhang, Xuewu
AU - Schwartz, Jean Claude D.
AU - Guo, Xiaoling
AU - Bhatia, Sumeena
AU - Cao, Erhu
AU - Chen, Lieping
AU - Zhang, Zhong Yin
AU - Edidin, Michael A.
AU - Nathenson, Stanley G.
AU - Almo, Steven C.
N1 - Funding Information:
We thank Dr. T. DiLorenzo and M. Roden for insightful discussions, Dr. Z. Dauter for assistance with data collection, and Dr. M. Brenowitz and S. Morris for assistance with analytical ultracentrifugation experiments. This work is supported by grants from the National Institutes of Health to L.C., M.A.E., S.G.N., and S.C.A. X.G. and Z.-Y.Z. are supported in part by the G. Harold and Leila Y. Mathers Charitable Foundation.
PY - 2004/3
Y1 - 2004/3
N2 - 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 Å 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.
AB - 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 Å 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.
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U2 - 10.1016/S1074-7613(04)00051-2
DO - 10.1016/S1074-7613(04)00051-2
M3 - Article
C2 - 15030777
AN - SCOPUS:12144290320
SN - 1074-7613
VL - 20
SP - 337
EP - 347
JO - Immunity
JF - Immunity
IS - 3
ER -