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Galectin-13 variant C136S
Structural highlights
FunctionPP13_HUMAN Binds beta-galactoside and lactose. Strong inducer of T-cell apoptosis.[1] [2] Publication Abstract from PubMedGalectin-13 (Gal-13) plays numerous roles in regulating the relationship between maternal and fetal tissues. Low expression levels or mutations of the lectin can result in pre-eclampsia. The previous crystal structure and gel filtration data show that Gal-13 dimerizes via formation of two disulfide bonds formed by Cys136 and Cys138. In the present study, we mutated them to serine (C136S, C138S and C136S/C138S), crystalized the variants and solved their crystal structures. All variants crystallized as monomers. In the C136S structure, Cys138 formed a disulfide bond with Cys19, indicating that Cys19 is important for regulation of reversible disulfide bond formation in this lectin. Hemagglutination assays demonstrated that all variants are inactive at inducing erythrocyte agglutination, even though gel filtration profiles indicate that C136S and C138S could still form dimers, suggesting that these dimers do not exhibit the same activity as wild type Gal-13. In HeLa cells, the three variants were found to be distributed the same as with wild type Gal-13. However, a Gal-13 variant truncated at T221 could not be transported into the nucleus, possibly explaining why women having this variant get pre-eclampsia. Considering the normally high concentration of glutathione in cells, wild type Gal-13 should exist mostly as a monomer in cytoplasm, consistent with the monomeric variant C136S/C138S which has a similar ability to interact with HOXA1 as wild type Gal-13. Galectin-13/placental protein 13: redox-active disulfides as switches for regulating structure, function and cellular distribution.,Yang T, Yao Y, Wang X, Li Y, Si Y, Li X, Ayala GJ, Wang Y, Mayo KH, Tai G, Zhou Y, Su J Glycobiology. 2019 Oct 4. pii: 5575951. doi: 10.1093/glycob/cwz081. PMID:31584064[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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