Structural highlights
Publication Abstract from PubMedCharcot-Leyden crystals (CLCs) are the hallmark of many eosinophilic-based diseases, such as asthma. Here, we report that reduced glutathione (GSH) disrupts CLCs and inhibits crystallization of human galectin-10 (Gal-10). GSH has no effect on CLCs from monkeys ( Macaca fascicularis or M. mulatta), even though monkey Gal-10s contain Cys29 and Cys32. Interestingly, human Gal-10 contains another cysteine residue (Cys57). Because GSH cannot disrupt CLCs formed by the human Gal-10 variant C57A or inhibit its crystallization, the effects of GSH on human Gal-10 or CLCs most likely occur by chemical modification of Cys57. We further report the crystal structures of Gal-10 from M. fascicularis and M. mulatta, along with their ability to bind to lactose and inhibit erythrocyte agglutination. Structural comparison with human Gal-10 shows that Cys57 and Gln75 within the ligand binding site are responsible for the loss of lactose binding. Pull-down experiments and mass spectrometry show that human Gal-10 interacts with tubulin alpha-1B, with GSH, GTP and Mg (2+) stabilizing this interaction and colchicine inhibiting it. Overall, this study enhances our understanding of Gal-10 function and CLC formation and suggests that GSH may be used as a pharmaceutical agent to ameliorate CLC-induced diseases. Glutathione disrupts galectin-10 Charcot-Leyden crystal formation to possibly ameliorate eosinophil-based diseases such as asthma.,Na H, Sayed H, Ayala GJ, Wang X, Liu Y, Yu J, Liu T, Mayo KH, Su J Acta Biochim Biophys Sin (Shanghai). 2023 Mar 25. doi: 10.3724/abbs.2023050. PMID:36988350[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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