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3bik
From Proteopedia
| 3bik, resolution 2.65Å () | |||||||||
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| Sites: | |||||||||
| Ligands: | |||||||||
| Gene: | CD274, B7H1, PDCD1L1, PDCD1LG1, PDL1 (Homo sapiens), Pdcd1, Pd1 (Mus musculus) | ||||||||
| Domains: | C2-set_2, V-set, IG | ||||||||
| Related: | 3bis | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Crystal Structure of the PD-1/PD-L1 Complex
Signaling through the programmed death 1 (PD-1) inhibitory receptor upon binding its ligand, PD-L1, suppresses immune responses against autoantigens and tumors and plays an important role in the maintenance of peripheral immune tolerance. Release from PD-1 inhibitory signaling revives "exhausted" virus-specific T cells in chronic viral infections. Here we present the crystal structure of murine PD-1 in complex with human PD-L1. PD-1 and PD-L1 interact through the conserved front and side of their Ig variable (IgV) domains, as do the IgV domains of antibodies and T cell receptors. This places the loops at the ends of the IgV domains on the same side of the PD-1/PD-L1 complex, forming a surface that is similar to the antigen-binding surface of antibodies and T cell receptors. Mapping conserved residues allowed the identification of residues that are important in forming the PD-1/PD-L1 interface. Based on the structure, we show that some reported loss-of-binding mutations involve the PD-1/PD-L1 interaction but that others compromise protein folding. The PD-1/PD-L1 interaction described here may be blocked by antibodies or by designed small-molecule drugs to lower inhibitory signaling that results in a stronger immune response. The immune receptor-like loops offer a new surface for further study and potentially the design of molecules that would affect PD-1/PD-L1 complex formation and thereby modulate the immune response.
The PD-1/PD-L1 complex resembles the antigen-binding Fv domains of antibodies and T cell receptors., Lin DY, Tanaka Y, Iwasaki M, Gittis AG, Su HP, Mikami B, Okazaki T, Honjo T, Minato N, Garboczi DN, Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3011-6. Epub 2008 Feb 14. PMID:18287011
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
3BIK is a 3 chains structure of sequences from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA.
Reference
- Lin DY, Tanaka Y, Iwasaki M, Gittis AG, Su HP, Mikami B, Okazaki T, Honjo T, Minato N, Garboczi DN. The PD-1/PD-L1 complex resembles the antigen-binding Fv domains of antibodies and T cell receptors. Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3011-6. Epub 2008 Feb 14. PMID:18287011
Page seeded by OCA on Tue Feb 17 07:05:52 2009
Categories: Homo sapiens | Mus musculus | Garboczi, D N. | Gittis, A G. | Honjo, T. | Iwasaki, M. | Lin, D Y. | Mikami, B. | Minato, N. | Okazaki, T. | Su, H P. | Tanaka, Y. | Alternative splicing | Apoptosis | B cell | Co-stimulation | Glycoprotein | Immune system | Immunoglobulin domain | Immunoglobulin-like beta-sandwich | Inhibitory receptor | Programmed death | Receptor-ligand complex | T cell | Transmembrane
