Science Sub-Journal: Ouyang Bo's team reveals the molecular mechanism of cholesterol regulating PD-L1 stability

Cholesterol is one of the main components of the body's cell membrane and regulates the fluidity and permeability of cell membranes

Many studies in recent years have shown that cholesterol can participate in regulating the structure and function of many membrane proteins by binding directly to membrane proteins, and identify multiple cholesterol-binding motifs

So, is there a direct link between high levels of cholesterol in tumor cells and highly expressed PD-L1, and does cholesterol play a regulatory role in PD-L1?

Recently, the Ouyang Bo Research Group of the Center for Excellence in Molecular and Cell Science (Institute of Biochemistry and Cell Biology) of the Chinese Academy of Sciences published a research paper

The study found that cholesterol molecules can bind directly to the two CRAC motifs of the PD-L1 transmembrane segment to form a "sandwich-like" structure that regulates the stability and degradation

The research team first proved through biochemical and cell function experiments that cholesterol can stabilize PD-L1 on the cell membrane, and the addition of the cholesterol-lowering drug simvastatin and the cholesterol scavenger methyl β cyclodextrin will reduce the level of PD-L1 on the cell membrane and enhance the degradation

Functional experiments have shown that removing both cholesterol and mutant cholesterol binding sites causeSYD-L1 to degrade more easily and levels of PD-L1 to decrease

Schematic diagram of cholesterol regulating PD-L1 stability and degradation

Dr.

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