6L8R

membrane-bound PD-L1-CD

6L8R の概要

• エントリーDOI: 10.2210/pdb6l8r/pdb
• NMR情報: BMRB: 36293
• 分子名称: Programmed cell death 1 ligand 1 (1 entity in total)
• 機能のキーワード: pd-l1, membrane-bound, cytoplasmic domain, stability, immunosuppressant
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 3797.37

構造登録者

Maorong, W.,Cao, Y.,Bin, W.,Bo, O. (登録日: 2019-11-07, 公開日: 2020-11-11, 最終更新日: 2024-05-15)

主引用文献

Wen, M.,Cao, Y.,Wu, B.,Xiao, T.,Cao, R.,Wang, Q.,Liu, X.,Xue, H.,Yu, Y.,Lin, J.,Xu, C.,Xu, J.,OuYang, B.
PD-L1 degradation is regulated by electrostatic membrane association of its cytoplasmic domain.
Nat Commun, 12:5106-5106, 2021

PubMed Abstract: The cytoplasmic domain of PD-L1 (PD-L1-CD) regulates PD-L1 degradation and stability through various mechanism, making it an attractive target for blocking PD-L1-related cancer signaling. Here, by using NMR and biochemical techniques we find that the membrane association of PD-L1-CD is mediated by electrostatic interactions between acidic phospholipids and basic residues in the N-terminal region. The absence of the acidic phospholipids and replacement of the basic residues with acidic residues abolish the membrane association. Moreover, the basic-to-acidic mutations also decrease the cellular abundance of PD-L1, implicating that the electrostatic interaction with the plasma membrane mediates the cellular levels of PD-L1. Interestingly, distinct from its reported function as an activator of AMPK in tumor cells, the type 2 diabetes drug metformin enhances the membrane dissociation of PD-L1-CD by disrupting the electrostatic interaction, thereby decreasing the cellular abundance of PD-L1. Collectively, our study reveals an unusual regulatory mechanism that controls the PD-L1 level in tumor cells, suggesting an alternative strategy to improve the efficacy of PD-L1-related immunotherapies.

PubMed: 34429434
DOI: 10.1038/s41467-021-25416-7

実験手法

SOLUTION NMR