title: Structural and functional analysis of the costimulatory receptor programmed death-1.
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.
authors.affiliation: Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461 USA.
authors.forename: Xuewu
authors.initials: X
authors.lastname: Zhang
authors.forename: Jean-Claude D
authors.initials: JC
authors.lastname: Schwartz
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Guo
authors.forename: Sumeena
authors.initials: S
authors.lastname: Bhatia
authors.forename: Erhu
authors.initials: E
authors.lastname: Cao
authors.forename: Michael
authors.initials: M
authors.lastname: Lorenz
authors.forename: Michael
authors.initials: M
authors.lastname: Cammer
authors.forename: Lieping
authors.initials: L
authors.lastname: Chen
authors.forename: Zhong-Yin
authors.initials: ZY
authors.lastname: Zhang
authors.forename: Michael A
authors.initials: MA
authors.lastname: Edidin
authors.forename: Stanley G
authors.initials: SG
authors.lastname: Nathenson
authors.forename: Steven C
authors.initials: SC
authors.lastname: Almo
mesh_terms: 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
chemical_list: 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