Abstract
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
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Antigens, CD
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Antigens, Differentiation / chemistry*
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Antigens, Differentiation / genetics
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Antigens, Differentiation / metabolism
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B7-1 Antigen / metabolism
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B7-H1 Antigen
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Blood Proteins*
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CTLA-4 Antigen
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Immunoglobulin Variable Region / chemistry
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Ligands
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Membrane Glycoproteins
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Mice
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Models, Molecular
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Molecular Sequence Data
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Mutation
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Peptides*
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Programmed Cell Death 1 Receptor
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Receptors, Immunologic / chemistry*
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Receptors, Immunologic / genetics
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Receptors, Immunologic / metabolism*
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Sequence Alignment
Substances
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Antigens, CD
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Antigens, Differentiation
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B7-1 Antigen
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B7-H1 Antigen
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Blood Proteins
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CTLA-4 Antigen
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Cd274 protein, mouse
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Ctla4 protein, mouse
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Immunoglobulin Variable Region
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Ligands
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Membrane Glycoproteins
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Pdcd1 protein, mouse
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Peptides
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Programmed Cell Death 1 Receptor
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Receptors, Immunologic