Galectin-13/placental protein 13: redox-active disulfides as switches for regulating structure, function and cellular
Tong Yang1, Yuan Yao2, Xing Wang1
1Jilin Province Key Laboratory for Chemistry and Biology of Natural Drugs in Changbai Mountain, The School of Life Sciences, Northeast Normal University, 5268 Renmin Street, Changchun 130024, China.
Glycobiology
|October 5, 2019
Summary
Galectin-13 (Gal-13) mutations affect its structure and function, impacting maternal-fetal health and potentially causing pre-eclampsia. Monomeric Gal-13 retains some interactions, suggesting a role in cellular processes.
Area of Science:
- Biochemistry
- Molecular Biology
- Reproductive Biology
Background:
- Galectin-13 (Gal-13) is crucial for maternal-fetal tissue interactions.
- Dysregulation of Gal-13 is linked to pre-eclampsia.
- Wild-type Gal-13 dimerizes through disulfide bonds involving Cys136 and Cys138.
Purpose of the Study:
- To investigate the structural and functional consequences of mutating Gal-13's key cysteine residues.
- To elucidate the role of specific cysteine residues in Gal-13 dimerization and activity.
- To explore the cellular localization and interaction capabilities of Gal-13 variants.
Main Methods:
- Site-directed mutagenesis of Gal-13 (C136S, C138S, C136S/C138S).
- X-ray crystallography to determine variant structures.
- Gel filtration and hemagglutination assays to assess dimerization and erythrocyte agglutination.
- Cellular localization studies in HeLa cells.
Main Results:
- All tested Gal-13 variants (C136S, C138S, C136S/C138S) crystallized as monomers.
- Cys19 was identified as a potential regulatory disulfide bond partner in the C136S variant.
- Mutant variants lost hemagglutination activity, though some retained dimerization capacity.
- A delT221 variant showed impaired nuclear transport, correlating with pre-eclampsia.
- Monomeric C136S/C138S variant exhibited similar HOXA1 interaction as wild-type Gal-13.
Conclusions:
- Disulfide bonds involving Cys136 and Cys138 are essential for Gal-13's erythrocyte agglutination activity.
- Cys19 plays a role in regulating Gal-13 disulfide bond formation.
- Impaired nuclear transport of Gal-13 variants may contribute to pre-eclampsia pathogenesis.
- Wild-type Gal-13 likely exists as a monomer in the cytoplasm, maintaining interactions with partners like HOXA1.
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