人白细胞介素-29的生物信息学分析

目的利用生物信息学技术对人白细胞介素-29(Human nterleukin-29,IL-29)进行分析,为定点突变hIL-29,以提高其生物学活性奠定理论基础。方法利用生物信息学技术分析克隆得到的hIL-29基因,预测hIL-29基因编码蛋白的理化性质、结构、功能及可能影响其生物学活性的关键氨基酸位点;预测其三维结构,并与IFNλ3的晶体结构进行比对;对检索到的9个物种的IL-29基因同源序列进行比对,并构建系统进化树。结果 hIL-29基因编码蛋白含200个氨基酸残基,其N-末端19个氨基酸为信号肽,成熟肽的相对分子质量为20 018,理论等电点为9.08,肽链中含一个由胞内向胞外的跨膜结构域;hIL-29的空间构象由6个α螺旋(A～F)和无规则卷曲组成,螺旋A、B和F可能是hIL-29与特异性受体结合而发挥生物学效应的活性部位,A、F螺旋中有4个氨基酸残基可能是影响其生物学活性的关键氨基酸位点;系统进化分析显示,hIL-29与狗、猫、大熊猫、马、野猪、黑猩猩、长臂猿的IL-29具有较高的同源性,处于同一个大分枝,而人、黑猩猩、长臂猿的IL-29处于同一个小分枝,在系统进化树中的距离最近。结论关键位点氨基酸的差异可能对hIL-29的生物学活性影响较大,可作为对hIL-29进行分子改造的突变位点。本研究为后续进行hIL-29的定向改构及其构效关系等的深入研究奠定了理论基础。

Bioinformatics of human interleukin-29

Objective To analyze the bioinformatics of human interleukin-29(hIL-29) and lay a foundation of directed mutation of hIL-29 so as to improve its bioactivity.Methods The cloned hIL-29 gene was analyzed by bioinformatics tools.The physicochemical characteristics,structures,functions,and the key amino acid sites of protein encoded by the gene were predicted.The three-dimensional structure of the protein was predicated and compared with the crystal structure of IFNλ3.The homologies of IL-29 genes of nine species were compared,based on which a phylogenetic tree was plotted.Results The protein encoded by hIL-29 gene consisted of 200 amino acids,with a signal peptide containing 19 amino acids at N-terminus.The relative molecular mass of mature peptide was 20 018,while the theoretical isoelectric point was 9.08.The hIL-29 protein contained an intracellular-extracellular transmembrane domain.The spatial conformation was composed with six α-helixes(A to F) and some random coils.The helixes A,B and F might be the activity sites in which hIL-29 was bound to its specific receptor and gave play to its biological effect.It was predicted that four key amino acid sites might exist in helixes A and F.The IL-29 from human origin were highly homologous to those form dog,cat,panda,horse,wild boar,chimpanzee and gibbon origins,which belonged to the same big branch on phylogenetic tree.However,the IL-29 gene from human,chimpanzee and gibbon origins belonged to the same small branch,of which the relationship was the closest.Conclusion The variation of amino acids at key sites might have significant effect on bioactivity of hIL-29,indicating that the sites might be used as the mutation sites for molecular modification of hIL-29.It laid a theoretical foundation of further study on directed mutation as well as relationship between structure and function of hIL-29.