8J3V

Structure of the transmembrane domain of human PD-L2

Summary for 8J3V

• Entry DOI: 10.2210/pdb8j3v/pdb
• Descriptor: Programmed cell death 1 ligand 2 (1 entity in total)
• Functional Keywords: pd-l2, transmembrane domain, tumor, ligand, immune system
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 6936.17

Authors

OuYang, B.,Zhang, Y. (deposition date: 2023-04-18, release date: 2024-03-13, Last modification date: 2024-05-15)

Primary citation

Zhang, Y.,Xiao, T.,Wen, M.,Shen, L.,Du, L.,Wei, S.,Wu, B.,Yu, Y.,Wang, S.,OuYang, B.
Deciphering Cholesterol's Role in PD-L2 Stability: A Distinct Regulatory Mechanism From PD-L1.
J.Mol.Biol., 436:168500-168500, 2024

PubMed Abstract: Programmed cell death 1 ligand 2 (PD-L2), a member of the B7 immune checkpoint protein family, emerges as a crucial player in immune modulation. Despite its functional overlap with programmed cell death 1 ligand 1 (PD-L1) in binding to the programmed cell death protein 1 (PD-1) on T cells, PD-L2 exhibits a divergent expression pattern and a higher affinity for PD-1. However, the regulatory mechanisms of PD-L2 remain under-explored. Here, our investigations illustrate the pivotal role of cholesterol in modulating PD-L2 stability. Using advanced nuclear magnetic resonance (NMR) and biochemical analyses, we demonstrate a direct and specific binding between cholesterol and PD-L2, mediated by an F-xxx-V-xx-LR motif in its transmembrane domain, distinct from that in PD-L1. This interaction stabilizes PD-L2 and prevents its downstream degradation. Disruption of this binding motif compromises PD-L2's cellular stability, underscoring its potential significance in cancer biology. These findings not only deepen our understanding of PD-L2 regulation in the context of tumors, but also open avenues for potential therapeutic interventions.

PubMed: 38401626
DOI: 10.1016/j.jmb.2024.168500

Experimental method

SOLUTION NMR