| 摘要: | 研究期間：10108~10207;In recent years, enzyme research has not only focused on protein functional studies, but has increasingly extended into protein structural analyses. X-ray crystallography still remains the most useful way to visualize proteins and nucleic acids at atomic resolution. Through study of proteins at the atomic level, structural mechanisms can be elucidated. Nowadays, an important trend in enzyme research is to combine the protein functional and the structural study with structural analyses using X-ray crystallography. Galectins belong to a family of lactins, that have at least one carbohydrate recognition domain (CRD) with conserved sequence elements and affinity for β -galactosides. Although the functions of these lectins are not yet fully understood, there is evidence that one or more are involved in growth regulation, cell adhesion, and cell migration and that they play roles in neoplasia and immune responses. To date, 17 members of the galectin family which are subdivided into three group types have been isolated from various tissues and cells in mammals. Galectin-12 was first discovered in 2001 by 2 independent groups and was predominantly expressed in adipose tissue and that galectin-12 possessed cellular apoptosis-inducing activity. Expression of galectin-12 was augmented in adipose tissue of animals undercaloric restriction and treatment with a synthetic peroxisome proliferator-activated receptor (PPAR)γligand, along with a decrease in average cell size in adipose tissue and improvement of insulin resistance. In addition, galectin-12 may also participate in apoptosis of adipocytes and glucose metabolism. According to the studies of Dr. Fu-Tong Liu (Director of the Institute of Biomedical Sciences, Academia Sinica) showed that galectin-12 depletion reduces adiposity and improves insulin sensitivity and glucose tolerance caused by increased body weight. Meanwhile, studies of Prof. Wan Lei in China Medical University in Tai-Chung found that galectin-12 is expressed in T-cells and macrophages, and that knocking out galectin-12 influences the polarization of T-cells toward Th1 and the differentiation of macrophages to M2 macrophages. Although researches have shown the importance of galectin-12 regulating involving biological function in adipocyte, protein expression and purification of galectin-12 in vitro still exists some challenges due to that galectin-12 is highly hydrophobic than any other galectins. In order to understand interactions between galectin-12 and other related proteins in adipocytes and also to uncover relationships between the protein function and the protein structure. Most important, none of the protein structure in type C galectin family members including galectin-12 so far has been determined Thus, this project will be focusing on efficiently protein purified, performing protein crystallization trails and protein structure determination |
