Sequence-specific 1H, 13C and 15N backbone NMR assignments for the N-terminal IgV-like domain (D1) and full extracellular region (D1D2) of PD-L1

Biomol NMR Assign. 2022 Oct;16(2):281-288. doi: 10.1007/s12104-022-10092-5. Epub 2022 Jun 8.

Abstract

The co-inhibitory immune checkpoint interaction between programmed cell death-protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) serves to regulate T-cell activation, promoting self-tolerance. Over-expression of PD-L1 is a mechanism through which tumour cells can evade detection by the immune system. Several therapeutic antibodies targeting PD-L1 or PD-1 have been approved for the treatment of a variety of cancers, however, the discovery and development of small-molecule inhibitors of PD-L1 remains a challenge. Here we report comprehensive sequence-specific backbone resonance assignments (1H, 13C, and 15N) obtained for the N-terminal IgV-like domain of PD-L1 (D1) and the full two domain extracellular region (D1D2). These NMR assignments will serve as a useful tool in the discovery of small-molecule therapeutics targeting PD-L1 and in the characterisation of functional interactions with other protein partners, such as CD80.

Keywords: Cancer; Immune checkpoint; Programmed cell death-ligand 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7-H1 Antigen / metabolism
  • B7-H1 Antigen / therapeutic use
  • Humans
  • Ligands
  • Neoplasms* / drug therapy
  • Neoplasms* / pathology
  • Nuclear Magnetic Resonance, Biomolecular
  • Programmed Cell Death 1 Receptor*

Substances

  • B7-H1 Antigen
  • Ligands
  • Programmed Cell Death 1 Receptor