TY - JOUR
T1 - Intestinal mucin is a chaperone of multivalent copper
AU - Reznik, Nava
AU - Gallo, Annastassia D.
AU - Rush, Katherine W.
AU - Javitt, Gabriel
AU - Fridmann-Sirkis, Yael
AU - Ilani, Tal
AU - Nairner, Noa A.
AU - Fishilevich, Simon
AU - Gokhman, David
AU - Chacón, Kelly N.
AU - Franz, Katherine J.
AU - Fass, Deborah
N1 - Publisher Copyright: © 2022 The Author(s)
PY - 2022/10/27
Y1 - 2022/10/27
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85140222788&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.cell.2022.09.021
DO - https://doi.org/10.1016/j.cell.2022.09.021
M3 - مقالة
C2 - 36206754
SN - 0092-8674
VL - 185
SP - 4206-4215.e11
JO - Cell
JF - Cell
IS - 22
ER -