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Human galectin-16 has a pseudo ligand binding site and plays a role in regulating c-Rel-mediated lymphocyte activity
Biochimica et Biophysica Acta (BBA) - General Subjects ( IF 3 ) Pub Date : 2020-10-02 , DOI: 10.1016/j.bbagen.2020.129755
Yunlong Si , Yuan Yao , Gabriela Jaramillo Ayala , Xumin Li , Qiuyu Han , Wenlu Zhang , Xuejiao Xu , Guihua Tai , Kevin H. Mayo , Yifa Zhou , Jiyong Su

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.



中文翻译:

人Galectin-16具有假配体结合位点,并在调节c-Rel介导的淋巴细胞活性中发挥作用

背景

人半乳凝素16(Gal-16)的结构尚未解决,其功能仍然难以捉摸。

方法

X射线晶体学用于确定Gal-16及其两个突变体的原子结构。通过凝胶过滤研究了Gal-16低聚物的状态,使用ITC测定了其血凝活性以及结合乳糖的能力。还研究了带有EGFP标签的Gal-16在各种细胞系中的细胞分布,并通过下拉研究,微型热泳和免疫荧光评估了Gal-16和c-Rel之间的相互作用。

结果

与其他半乳凝素不同,Gal-16缺乏结合β-半乳糖苷乳糖的能力。乳糖结合可以通过用天冬酰胺替代精氨酸(Arg55)来恢复,如两个乳糖加载的Gal-16突变体(R55N和R55N / H57R)的晶体结构所示。Gal-16还通过凝胶过滤和晶体结构显示为单体。因此,该半乳糖凝集素不能诱导红细胞凝集。发现带有EGFP标签的Gal-16主要位于各种细胞类型的细胞核中,并且可以与NF-κB家族成员c-Rel相互作用。

结论

Gal-16以单体形式存在,并且其配体结合与其他原型半乳凝素的配体结合显着不同,表明它具有新颖的功能。Gal-16和c-Rel之间的相互作用表明,Gal-16可能通过母婴界面B或T细胞中的c-Rel集线器调节信号转导途径。

一般意义

本研究为进一步研究Gal-16的细胞和生理功能奠定了基础。

更新日期:2020-10-11
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