Leicester Institute of Structural and Chemical Biology, Leicester, UK.
Department of Molecular and Cell Biology, University of Leicester, Henry Wellcome Building, Lancaster Road, Leicester, LE1 7HB, UK.
Biomol NMR Assign. 2022 Oct;16(2):281-288. doi: 10.1007/s12104-022-10092-5. Epub 2022 Jun 8.
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 (H, C, and N) 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.
程序性死亡蛋白 1(PD-1)和程序性死亡配体 1(PD-L1)之间的共抑制免疫检查点相互作用可调节 T 细胞的激活,促进自身耐受。PD-L1 的过度表达是肿瘤细胞逃避免疫系统检测的一种机制。几种针对 PD-L1 或 PD-1 的治疗性抗体已被批准用于治疗多种癌症,但 PD-L1 的小分子抑制剂的发现和开发仍然是一个挑战。在这里,我们报告了 PD-L1(D1)的 N 端 IgV 样结构域和完整的两个结构域外区(D1D2)的全面序列特异性骨架共振分配(H、C 和 N)。这些 NMR 分配将作为发现针对 PD-L1 的小分子治疗药物以及与其他蛋白伴侣(如 CD80)的功能相互作用的特征的有用工具。