3BIS

Crystal Structure of the PD-L1

Summary for 3BIS

• Entry DOI: 10.2210/pdb3bis/pdb
• Related: 3BIK
• Descriptor: Programmed cell death 1 ligand 1 (2 entities in total)
• Functional Keywords: co-stimulation, immunoglobulin-like beta-sandwich, t cell, b cell, programmed death, immune system, transmembrane, inhibitory receptor, glycoprotein, immunoglobulin domain
• Biological source: Homo sapiens (human)
• Cellular location: Isoform 1: Cell membrane; Single-pass type I membrane protein. Isoform 2: Endomembrane system; Single-pass type I membrane protein: Q9NZQ7
• Total number of polymer chains: 2
• Total formula weight: 50793.56

Authors

Lin, D.Y.,Tanaka, Y.,Iwasaki, M.,Gittis, A.G.,Su, H.P.,Mikami, B.,Okazaki, T.,Honjo, T.,Minato, N.,Garboczi, D.N. (deposition date: 2007-11-30, release date: 2008-02-26, Last modification date: 2024-11-20)

Primary citation

Lin, D.Y.,Tanaka, Y.,Iwasaki, M.,Gittis, A.G.,Su, H.P.,Mikami, B.,Okazaki, T.,Honjo, T.,Minato, N.,Garboczi, D.N.
The PD-1/PD-L1 complex resembles the antigen-binding Fv domains of antibodies and T cell receptors.
Proc.Natl.Acad.Sci.Usa, 105:3011-3016, 2008

PubMed Abstract: 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.

PubMed: 18287011
DOI: 10.1073/pnas.0712278105

Experimental method

X-RAY DIFFRACTION (2.64 Å)