Crystal structure of the complex between programmed death-1 (PD-1) and its ligand PD-L2

Eszter Lázár-Molnár, Qingrong Yan, Erhu Cao, Udupi Ramagopal, Stanley G. Nathenson, Steven C. Almo

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

Programmed death-1 (PD-1) is a member of the CD28/B7 superfamily that delivers negative signals upon interaction with its two ligands, PD-L1 or PD-L2. The high-resolution crystal structure of the complex formed by the complete ectodomains of murine PD-1 and PD-L2 revealed a 1:1 receptor:ligand stoichiometry and displayed a binding interface and overall molecular organization distinct from that observed in the CTLA-4/B7 inhibitory complexes. Furthermore, our structure also provides insights into the association between PD-1 and PD-L1 and highlights differences in the interfaces formed by the two PD-1 ligands (PD-Ls) Mutagenesis studies confirmed the details of the proposed PD-1/PD-L binding interfaces and allowed for the design of a mutant PD-1 receptor with enhanced affinity. These studies define spatial and organizational constraints that control the localization and signaling of PD-1/PD-L complexes within the immunological synapse and provide a basis for manipulating the PD-1 pathways for immunotherapy.

Original languageEnglish (US)
Pages (from-to)10483-10488
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number30
DOIs
StatePublished - Jul 29 2008

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Programmed Cell Death 1 Ligand 2 Protein
Ligands
Immunological Synapses
Death Domain Receptors
Mutagenesis
Immunotherapy

Keywords

  • Coinhibition
  • Costimulation
  • Inhibitory receptor
  • T cell activation

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Crystal structure of the complex between programmed death-1 (PD-1) and its ligand PD-L2. / Lázár-Molnár, Eszter; Yan, Qingrong; Cao, Erhu; Ramagopal, Udupi; Nathenson, Stanley G.; Almo, Steven C.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 30, 29.07.2008, p. 10483-10488.

Research output: Contribution to journalArticle

Lázár-Molnár, Eszter ; Yan, Qingrong ; Cao, Erhu ; Ramagopal, Udupi ; Nathenson, Stanley G. ; Almo, Steven C. / Crystal structure of the complex between programmed death-1 (PD-1) and its ligand PD-L2. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 30. pp. 10483-10488.
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AU - Nathenson, Stanley G.

AU - Almo, Steven C.

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