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

185 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
Externally publishedYes

Fingerprint

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Zhang, X., Schwartz, J. C. D., Guo, X., Bhatia, S., Cao, E., Chen, L., ... Almo, S. C. (2004). Structural and functional analysis of the costimulatory receptor programmed death-1. Immunity, 20(3), 337-347. https://doi.org/10.1016/S1074-7613(04)00051-2

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, Z-Y, 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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