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PDBsum entry 3bp5
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Signaling protein
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PDB id
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3bp5
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References listed in PDB file
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Key reference
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Title
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Crystal structure of the complex between programmed death-1 (pd-1) and its ligand pd-L2.
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Authors
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E.Lázár-Molnár,
Q.Yan,
E.Cao,
U.Ramagopal,
S.G.Nathenson,
S.C.Almo.
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Ref.
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Proc Natl Acad Sci U S A, 2008,
105,
10483-10488.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Figure 1.
Structure of the PD-1/PD-L2 complex. (A) Overall structure of
the PD-1/PD-L2 complex. Green, PD-1; cyan, PD-L2. The strands of
PD-1 and PD-L2 are labeled in red and blue, respectively. (B)
Surface representation of PD-1/PD-L2 binding interface. Red,
hydrophilic residues in the binding interface; yellow,
hydrophobic residues in the binding interface. PD-L2 is in the
same orientation as in A; PD-1 is rotated 180° about a
vertical axis to reveal the binding surface.
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Figure 6.
PD-1/PD-L interaction at the cell–cell interface.
Noncovalent interactions between PD-1 and PD-Ls are sufficient
to drive their enrichment at a pseudosynapse. (A and B) PD-1 and
PD-L1 (A) or PD-L2 (B) expressed in CHO cells are recruited to
the cell–cell contact area and form conjugates that are
analogous to the immunological synapse. (Left)
PD-1-CFP-expressing cells in blue. (Center) PD-L1-YFP or
PD-L2-YFP-expressing cells in yellow. (Right) Overlay of the CFP
and YFP images. (C) Model of the PD-1/PD-L2 complex in the
immunological synapse. A number of receptor–ligand assemblies
have dimensions that are compatible with colocalization to the
central zone of the immunological synapse.
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