6KJW

Galectin-13 variant C136S

6KJW の概要

• エントリーDOI: 10.2210/pdb6kjw/pdb
• 分子名称: Galactoside-binding soluble lectin 13 (2 entities in total)
• 機能のキーワード: galectin-13 variant c136s, sugar binding protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16401.73

構造登録者

Su, J. (登録日: 2019-07-23, 公開日: 2019-10-16, 最終更新日: 2024-10-16)

主引用文献

Yang, T.,Yao, Y.,Wang, X.,Li, Y.,Si, Y.,Li, X.,Ayala, G.J.,Wang, Y.,Mayo, K.H.,Tai, G.,Zhou, Y.,Su, J.
Galectin-13/placental protein 13: redox-active disulfides as switches for regulating structure, function and cellular distribution.
Glycobiology, 30:120-129, 2020

PubMed Abstract: Galectin-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 (WT) Gal-13. In HeLa cells, the three variants were found to be distributed the same as with WT Gal-13. However, a Gal-13 variant (delT221) 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, WT 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 WT Gal-13.

PubMed: 31584064
DOI: 10.1093/glycob/cwz081

実験手法

X-RAY DIFFRACTION (1.36 Å)