胰岛素样生长因子受体Ⅰ序列结构的生物信息学分析

Bioinformatics analysis of sequence and structure of insulin-like growth factor-I receptor

摘要:

胰岛素样生长因子受体Ⅰ的 3'UTR长度大于7 kb，结构复杂，有多种miRNAs的结合位点，参与信号通路中MAPK及PI3K/AKT的调节和多种肿瘤的形成和发展，通过生物信息学分析知道其结构特点，为后续研究提供思路。分析表明儿童神经胶质瘤中IGF1R的3'UTR与miRNAs结合位点突变率最高。分析IGF1R序列3'UTR的结构，miRNAs结合位点，氨基酸序列的理化性质，亲疏水性，糖基化和磷酸化位点，二级结构和三级结构建模。IGF1R三级结构与配体IGF1的三级结构模拟分子对接，得到2种蛋白相互作用的氨基酸位置及名称。因此，通过对IGF1R 3'UTR突变，降低与miRNAs的结合，IGF1R表达上调，同时改变与IGF1的氨基酸结合位点，降低2种蛋白的相互作用，从而抑制IGF1R的作用。

Abstract:

The length of IGF1R 3’UTR is greater than 7 kb. The structure of IGF1R 3’UTR is complex, with multiple binding sites of miRNAs. IGF1R is involved in the regulation of MAPK and PI3K/AKT signaling pathways and the formation and development of tumors. Bioinformatics analysis can reveal the structure features of IGF1R, which provides ideas for further research. The analysis shows that the binding sites between IGF1R and miRNAs have the highest mutation rate in Neuroblastoma. We analyzed the structure of 3'UTR, miRNAs binding sites, physical and chemical properties, hydrophilic-hydrophobic property, glycosylation and phosphorylation sites, secondary structure and tertiary structure modeling of IGF1R. The locations and names of amino acids interacting in IGF1R and IGF1 were obtained by molecular docking. Therefore, if IGF1R 3'UTR is mutated, the capacity of IGF1R combined with miRNAs will reduce and the IGF1R expression will be up-regulated, and the function of miRNAs will be repressed. We can change the sites of IGF1R to combine with IGF1 to repress the function of IGF1R and IGF1. Then the function of IGF1R will be repressed.