PDBsum entry 3bp5

Signaling protein

PDB id: 3bp5

Contents

Protein chains

114 a.a. *

191 a.a. *

Ligands

GOL

Waters ×149

* Residue conservation analysis

PDB id:

3bp5

Name:

Signaling protein

Title:

Crystal structure of the mouse pd-1 and pd-l2 complex

Structure:

Programmed cell death protein 1. Chain: a. Fragment: extrocellular domain. Synonym: protein pd-1, mpd-1, cd279 antigen. Engineered: yes. Mutation: yes. Programmed cell death 1 ligand 2. Chain: b. Fragment: extrocellular domain.

Source:

Mus musculus. Mouse. Gene: pdcd1, pd1. Expressed in: escherichia coli. Gene: pdcd1lg2, b7dc, btdc, cd273, pdl2.

Resolution:

1.80Å R-factor: 0.192 R-free: 0.228

Authors:

Q.Yan,E.Lazar-Molnar,E.Cao,U.A.Ramagopal,R.Toro,S.G.Nathenson, S.C.Almo

Key ref:

E.Lázár-Molnár et al. (2008). Crystal structure of the complex between programmed death-1 (PD-1) and its ligand PD-L2. Proc Natl Acad Sci U S A, 105, 10483-10488. PubMed id: 18641123 DOI: 10.1073/pnas.0804453105

Date:

18-Dec-07 Release date: 15-Jul-08

Protein chain

Q02242  (PDCD1_MOUSE) -  Programmed cell death protein 1 from Mus musculus

Seq: 288 a.a.

Struc: 114 a.a.*

Protein chain

Q9WUL5  (PD1L2_MOUSE) -  Programmed cell death 1 ligand 2 from Mus musculus

Seq: 247 a.a.

Struc: 191 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1073/pnas.0804453105

Proc Natl Acad Sci U S A 105:10483-10488 (2008)

PubMed id: 18641123

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

E.Lázár-Molnár, Q.Yan, E.Cao, U.Ramagopal, S.G.Nathenson, S.C.Almo.

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.

Selected figure(s)

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.

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.

Figures were selected by an automated process.