Binding of Glycerol to Human Galectin-7 Expands Stability and Modulates Its Functions

Glycerol is seen in biological systems as an intermediate in lipid metabolism. In recent years, glycerol has been reported to act as a chemical chaperone to correct the conformation of proteins. Here, we investigate the role of glycerol in galectin-7 (Gal-7). The thermal shift and CD assays showed that the thermal stability of Gal-7 increased with glycerol concentration but with little secondary structure changes induced by glycerol. In addition, glycerol can inhibit Gal-7-mediated erythrocyte agglutination. We also solved the crystal structures of human Gal-7 in complex with glycerol in two different conditions. Glycerol binds at the carbohydrate-recognition binding sites of Gal-7, which indicates glycerol as a small ligand for Gal-7. Surprisingly, glycerol can bind a new pocket near the N-terminus of Gal-7, which can greatly reduce the flexibility and improve the stability of this region. Moreover, overexpression of Gal-7 decreased the intracellular triglyceride levels and increased mRNA expression of aquaporin-3 (AQP-3) when HeLa cells were incubated with glycerol. These findings indicate that Gal-7 might regulate glycerol metabolism. Overall, our results on human Gal-7 raise the perspective to systematically explore this so far unrecognized phenomenon for Gal-7 in glycerol metabolism.

Automated summary

Glycerol is an intermediate in lipid metabolism and has been found to act as a chemical chaperone for protein conformation. This study investigates the role of glycerol in Gal-7 and demonstrates that glycerol increases the thermal stability of Gal-7 and inhibits erythrocyte agglutination. Crystal structures reveal glycerol binding sites in Gal-7, suggesting its potential as a ligand for Gal-7. Overexpression of Gal-7 also affects glycerol metabolism and triglyceride levels in cells.