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.

中文翻译：

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Galectin-13 /胎盘蛋白13：氧化还原活性二硫化物，作为调节结构，功能和细胞分布的开关。

Galectin-13（Gal-13）在调节母体和胎儿组织之间的关系方面起着许多作用。凝集素的低表达水平或突变可导致先兆子痫。先前的晶体结构和凝胶过滤数据表明，Gal-13通过形成两个由Cys136和Cys138形成的二硫键而二聚。在本研究中，我们将它们突变为丝氨酸（C136S，C138S和C136S / C138S），使变体结晶并解决了其晶体结构。所有变体结晶为单体。在C136S结构中，Cys138与Cys19形成了二硫键，表明Cys19对于调节该凝集素中可逆二硫键的形成很重要。血凝试验表明，所有变体在诱导红细胞凝集时均无活性，即使凝胶过滤曲线表明C136S和C138S仍可以形成二聚体，表明这些二聚体与野生型（WT）Gal-13的活性不同。在HeLa细胞中，发现这三种变体的分布与WT Gal-13相同。然而，在T221处被截断的Gal-13变体（delT221）无法转运到细胞核中，这可能解释了为什么具有该变体的女性会先兆子痫。考虑到细胞中谷胱甘肽的正常高浓度，WT Gal-13应该主要作为单体存在于细胞质中，这与单体变体C136S / C138S一致，后者具有与WT Gal-13相似的与HOXA1相互作用的能力。发现这三个变体的分布与WT Gal-13相同。然而，在T221处被截断的Gal-13变体（delT221）无法转运到细胞核中，这可能解释了为什么具有该变体的女性会先兆子痫。考虑到细胞中谷胱甘肽的正常高浓度，WT Gal-13应该主要作为单体存在于细胞质中，这与单体变体C136S / C138S一致，后者具有与WT Gal-13相似的与HOXA1相互作用的能力。发现这三个变体的分布与WT Gal-13相同。然而，在T221处被截断的Gal-13变体（delT221）无法转运到细胞核中，这可能解释了为什么具有该变体的女性会先兆子痫。考虑到细胞中谷胱甘肽的正常高浓度，WT Gal-13应该主要作为单体存在于细胞质中，这与单体变体C136S / C138S一致，后者具有与WT Gal-13相似的与HOXA1相互作用的能力。