Structural and functional analysis of the costimulatory receptor programmed death-1

Xuewu Zhang, Jean Claude D Schwartz, Xiaoling Guo, Sumeena Bhatia, Erhu Cao, Lieping Chen, Zhong Yin Zhang, Michael A. Edidin, Stanley G. Nathenson, Steven C. Almo

Research output: Contribution to journalArticle

198 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)337-347
Number of pages11
JournalImmunity
Volume20
Issue number3
DOIs
StatePublished - Mar 2004

Fingerprint

Death Domain Receptors
Mutagenesis
Disulfides
Immunity
B-Lymphocytes
Ligands
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Structural and functional analysis of the costimulatory receptor programmed death-1. / Zhang, Xuewu; Schwartz, Jean Claude D; Guo, Xiaoling; Bhatia, Sumeena; Cao, Erhu; Chen, Lieping; Zhang, Zhong Yin; Edidin, Michael A.; Nathenson, Stanley G.; Almo, Steven C.

In: Immunity, Vol. 20, No. 3, 03.2004, p. 337-347.

Research output: Contribution to journalArticle

Zhang, X, Schwartz, JCD, Guo, X, Bhatia, S, Cao, E, Chen, L, Zhang, ZY, Edidin, MA, Nathenson, SG & Almo, SC 2004, 'Structural and functional analysis of the costimulatory receptor programmed death-1', Immunity, vol. 20, no. 3, pp. 337-347. https://doi.org/10.1016/S1074-7613(04)00051-2
Zhang, Xuewu ; Schwartz, Jean Claude D ; Guo, Xiaoling ; Bhatia, Sumeena ; Cao, Erhu ; Chen, Lieping ; Zhang, Zhong Yin ; Edidin, Michael A. ; Nathenson, Stanley G. ; Almo, Steven C. / Structural and functional analysis of the costimulatory receptor programmed death-1. In: Immunity. 2004 ; Vol. 20, No. 3. pp. 337-347.
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