期刊
CELL
卷 185, 期 22, 页码 4206-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2022.09.021
关键词
-
资金
- Israel Science Foundation
- Minerva Foundation
- Center for Scientific Excellence at the Weizmann Institute of Science
- US National Science Foundation
- U.S.-Israel Binational Science Foundation (ISF)
- [2660/20]
- [136813]
- [CHE-1808710]
- [2021097]
This study reveals the protective role of mucus in managing toxic transition metal copper by blocking futile redox cycling while allowing copper uptake into cells. The importance of molecular structure in advancing mucosal biology is highlighted, introducing mucins as extracellular copper chaperones produced in massive quantities to guard extensive mucosal surfaces.
Mucus protects the epithelial cells of the digestive and respiratory tracts from pathogens and other hazards. Progress in determining the molecular mechanisms of mucus barrier function has been limited by the lack of high-resolution structural information on mucins, the giant, secreted, gel-forming glycoproteins that are the major constituents of mucus. Here, we report how mucin structures we determined enabled the discovery of an unanticipated protective role of mucus: managing the toxic transition metal copper. Using two juxtaposed copper binding sites, one for Cu2+ and the other for Cu1+, the intestinal mucin, MUC2, prevents copper toxicity by blocking futile redox cycling and the squandering of dietary antioxidants, while nevertheless permitting uptake of this important trace metal into cells. These findings emphasize the value of molecular structure in advancing mucosal biology, while introducing mucins, produced in massive quantities to guard extensive mucosal surfaces, as extracellular copper chaperones.
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