AI Article Synopsis
- Charcot-Leyden crystals (CLCs) are associated with eosinophilic diseases like asthma, and the study reveals that reduced glutathione (GSH) disrupts CLCs by inhibiting the crystallization of human galectin-10 (Gal-10).
- GSH does not affect CLCs from monkeys, indicating that the human Gal-10 variant's unique cysteine (Cys57) is likely key to GSH's effects, as it doesn't disrupt crystallization of Gal-10 variants without this residue.
- The research also shows that human Gal-10 interacts with tubulin and is influenced by GSH, GTP, and Mg, suggesting potential pharmaceutical applications of GSH in treating diseases related to C
Article Abstract
Charcot-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 ( or ), 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 . and . , 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 α-1B, with GSH, GTP and Mg 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10195141 | PMC |
| http://dx.doi.org/10.3724/abbs.2023050 | DOI Listing |
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