Immunity
Volume 20, Issue 3, March 2004, Pages 337-347
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Article
Structural and Functional Analysis of the Costimulatory Receptor Programmed Death-1

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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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These authors contributed equally to this work.

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Present address: Xuewu Zhang, Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkley, Berkeley, California 94720.

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Present address: Jean-Claude D. Schwartz, Department of Surgery, Emory University Hospital, Atlanta, Georgia 30322.