哺乳动物MHCⅠ类分子α链的信号肽预测及保守性分析

Signal peptide prediction and conservation analysis of alpha chain of mammalian MHC class Ⅰ molecules

目的主要组织相容性复合体(major histocompatibility complex,MHC)由一紧密连锁、高度多态的基因座组成,在脊椎动物的移植排斥反应、免疫应答和免疫调控等方面发挥极其重要的作用。MHCⅠ类分子由α链和β微球蛋白以非共价键结合组成,其中α链直接参与抗原肽的呈递,显示极为丰富的多态性。本研究旨在分析哺乳动物MHCⅠ类分子α链的信号肽是否呈现出多态性,并明确其分子生物学特征。方法利用NCBI网站收集人等8种哺乳动物编码MHCⅠ类分子α链的mRNA序列,采用信号肽在线预测软件SignalP 4.1和LipoP1.0分析α链信号肽存在的概率、长度及信号肽酶切位点;利用Mega4.1软件进行信号肽氨基酸序列比对,分析其保守性。结果 8种哺乳动物MHCⅠ类分子α链N端的前24个氨基酸均为其信号肽区,信号肽酶切位点全部属于信号肽酶Ⅰ型,且信号肽酶切位点的-3、-1、1、2、3位置上的氨基酸非常保守,是信号肽酶识别的关键位点。氨基酸序列比对分析发现α链信号肽24个氨基酸中有13个位点的氨基酸相同,占信号肽氨基酸总数的54.17%。结论 8种哺乳动物MHCⅠ类分子α链的信号肽具有较强的保守性,这可能与信号肽指导蛋白质分选和蛋白质定位的功能相关。

Objective MHC（major histocompatibility complex） class Ⅰ molecules are mainly involved in the presentation of endogenous antigen peptides, the alpha-chain and beta-microglobulin are non-covalent interaction, and the alpha chain shows extremely abundant polymorphisms. The purpose of this study is to analyze the polymorphism of the MHCⅠ signal peptide of the alpha-chain of mammalian species, and clarify its molecular biological characteristics. Methods NCBI website was used to collect mRNA sequences of eight mammalian MHC class Ⅰ alpha-chains. The signal peptide online prediction software SignalP 4.1 and LipoP1.0 were used to analyze the probability length and the signal peptide enzyme cutting sites of alpha-chain signal peptide. The Mega4.1 software was used to compare the signal peptide amino acid sequence alignment and its conservation. Results The first 24 amino acids of the alpha-chain at the N-terminus of the eight mammalian MHC class Ⅰ molecules were all their signal peptide regions, and the signal peptidase sites all belonged to the signal peptidase Ⅰ type. The amino acids at positions-3,-1, 1, 2, and 3 were highly conserved and were key sites for signal peptidase recognition. Amino acid sequence alignment analysis revealed that there were 13 identical amino acids in the 24 amino acids of the alpha-chain signal peptide accounted for 54.17% of the total number of amino acids in the signal peptide.Conclusion The signal peptides of the alpha-chain of the eight mammalian MHC class Ⅰ molecules are highly conserved,which may be related to the function of the signal peptides in guiding protein sorting and protein localization.