6L8R

membrane-bound PD-L1-CD


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 200 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

PD-L1 degradation is regulated by electrostatic membrane association of its cytoplasmic domain.

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.

(2021) Nat Commun 12: 5106-5106

  • DOI: https://doi.org/10.1038/s41467-021-25416-7
  • Primary Citation of Related Structures:  
    6L8R

  • 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.


  • Organizational Affiliation

    State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China. mrwen@sibcb.ac.cn.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Programmed cell death 1 ligand 133Homo sapiensMutation(s): 0 
Gene Names: CD274B7H1PDCD1L1PDCD1LG1PDL1
UniProt & NIH Common Fund Data Resources
Find proteins for Q9NZQ7 (Homo sapiens)
Explore Q9NZQ7 
Go to UniProtKB:  Q9NZQ7
PHAROS:  Q9NZQ7
GTEx:  ENSG00000120217 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9NZQ7
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 200 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Natural Science Foundation of China (NSFC)China31861133009

Revision History  (Full details and data files)

  • Version 1.0: 2020-11-11
    Type: Initial release
  • Version 1.1: 2021-05-12
    Changes: Structure summary
  • Version 1.2: 2021-11-24
    Changes: Database references
  • Version 1.3: 2023-06-14
    Changes: Other
  • Version 1.4: 2024-05-15
    Changes: Data collection, Database references