Human galectin-16 has a pseudo ligand binding site and plays a role in regulating c-Rel-mediated lymphocyte activity

Autor: Yifa Zhou, Xuejiao Xu, Kevin H. Mayo, Guihua Tai, Qiuyu Han, Yuan Yao, Wenlu Zhang, Gabriela Jaramillo Ayala, Xumin Li, Jiyong Su, Yunlong Si
Rok vydání: 2020
Předmět:
Zdroj: Biochimica et biophysica acta. General subjects. 1865(1)
ISSN: 1872-8006
Popis: Background The structure of human galectin-16 (Gal-16) has yet to be solved, and its function has remained elusive. Methods X-ray crystallography was used to determine the atomic structures of Gal-16 and two of its mutants. The Gal-16 oligomer state was investigated by gel filtration, its hemagglutination activity was determined along with its ability to bind lactose using ITC. The cellular distribution of EGFP-tagged Gal-16 in various cell lines was also investigated, and the interaction between Gal-16 and c-Rel was assessed by pull-down studies, microscale thermophoresis and immunofluorescence. Results Unlike other galectins, Gal-16 lacks the ability to bind the β-galactoside lactose. Lactose binding could be regained by replacing an arginine (Arg55) with asparagine, as shown in the crystal structures of two lactose-loaded Gal-16 mutants (R55N and R55N/H57R). Gal-16 was also shown to be monomeric by gel filtration, as well as in crystal structures. Thus, this galectin could not induce erythrocyte agglutination. EGFP-tagged Gal-16 was found to be localized mostly in the nucleus of various cell types, and can interact with c-Rel, a member of NF-κB family. Conclusions Gal-16 exists as a monomer and its ligand binding is significantly different from that of other prototype galectins, suggesting that it has a novel function(s). The interaction between Gal-16 and c-Rel indicates that Gal-16 may regulate signal transduction pathways via the c-Rel hub in B or T cells at the maternal-fetal interface. General significance The present study lays the foundation for further studies into the cellular and physiological functions of Gal-16.
Databáze: OpenAIRE
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