原纤维蛋白1 C末端的系统发育和活性位点预测生物信息学分析

Bioinformatic Analysis of Phylogeny and Active Site Prediction of Fibrillin-1 C-terminus

人前原纤维蛋白1(profibrillin-1,FBN1)经过弗林蛋白酶(furin)酶切后得到成熟的原纤维蛋白-1和C末端多肽白脂素(asprosin),白脂素是新发现的参与调解糖代谢的热点激素。本研究采用整合生物信息学方法,对FBN1 C末端的系统发育和白脂素的功能位点进行分析,探究白脂素在糖代谢相关疾病发生中的分子机制。从UniProt数据库中搜索物种FBN1序列信息并进行比对;通过blastp方法检索脊椎动物FBN1 C末端氨基酸,构建进化树和进化轨迹,进行系统发育生物信息学分析;运用I-TASSER构建白脂素三级结构预测模型;运用COFACTOR和COACH法进行白脂素的配体活性位点分析。本研究发现:脊椎动物FBN1 C末端具有Furin酶识别位点(R-X-K/X-R)的高保守性,进化树结果显示FBN1 C末端蛋白有26个高保守位点,白脂素活性位点预测为“4RL”和“MAN”。本研究首次揭示原纤维蛋白1 C末端蛋白可能在脊椎动物中广泛存在,分析了白脂素的功能和结构的关系,为其在糖代谢性疾病中的功能机制研究和治疗提供新的思路。

Mature fibrillin-1 and a C-terminal peptide asprosin are products after the furin cleavage on profibrillin-1.Asprosin is a novel hormone widely investigated in glucose metabolism.The phylogeny analysis of FBN1 C-terminus and functional site analysis of asprosin were carried out using integrated bioinformatics methods.The molecular mechanism of asprosin was further explored in diseases related to glucose metabolism.FBN1 sequences of species were identified from the UniProt database for alinement.The sequence of C-terminal amino acid of vertebrate FBN1 was retrieved by blastp method.The evolutionary tree and trace were then constructed for bioinformatics analysis.Latent tertiary asprosin structure was constructed using I-TASSER and the active binding site was analyzed with the COFACTOR and COACH method.Our study found that the vertebrate FBN1 C-terminus had a high conservative property of furin recognition site(R-X-K/X-R).Our results showed that the C-terminal protein of FBN1 had 26 conserved sites.The active site of asprosin was predicted to be"4 RL"and MAN".This study indicates that the C-terminal protein of FBN1 is widely expressed in vertebrates.The results reveal the relationship of function and structure of asprosin and provide a reference for the study of the mechanism and treatment for glucose metabolism disorders.