梅毒螺旋体M23家族金属蛋白酶生物信息学分析

Bioinformatic analysis of M23 family metalloproteinases of Treponema pallidum

目的梅毒螺旋体可自由穿越血管壁,并可穿越血脑屏障和胎盘屏障,具有很强的侵袭力,但其侵袭的物质基础和分子机制不明。以往报道M23家族金属酶能够水解多种细胞外基质分子,对血管的主要成分弹性蛋白具有高度水解活性。本文采用生物信息学分析梅毒螺旋体M23家族金属蛋白酶基因结构和功能,为进一步研究其在梅毒螺旋体致病过程的作用提供理论基础。方法使用NCBI、CDD、MEROPS、SWISS-MODEL、CDTree、TMHMM、SignalP 4.1、ABCpred分析梅毒螺旋体M23家族金属蛋白酶的保守功能域、理化性质、跨膜区、信号肽、糖基化和磷酸化位点、空间结构以及抗原表位等。结果确定了梅毒螺旋体全基因组序列含有6个M23家族金属蛋白酶基因M23-MP1-6,除M23-MP5外均含有HXH结构域,M23-MP1-6基因编码蛋白均含有M23蛋白家族特征性结构域和磷酸化位点,M23-MP1、2和6均含有1个明显的跨膜结构,仅M23-MP4在第17位和18位氨基酸之间可能存在剪切位点,其余蛋白均不含信号肽。M23-MP1-6均含有B细胞表位和T细胞表位。结论梅毒螺旋体含有6个M23家族金属蛋白酶基因M23-MP1-6,提示梅毒螺旋体侵入宿主时,这些M23金属蛋白酶基因产物极有可能通过水解弹性蛋白来破坏宿主细胞间连接,改变血管壁、血脑屏障等通透性,从而促使梅毒螺旋体在宿主体内播散。

Objective Treponema pallidum can freely cross the vascular wall,blood-brain barrier and placental barrier,and has strong invasiveness,but the material basis and molecular mechanism of its invasion are unknown.It has been reported that M23 family metalloenzymes can hydrolyze a variety of extracellular matrix molecules and have high hydrolysis activity for elastin,the main component of blood vessels.In this study,bioinformatics was used to analyze the gene structure and function of M23 family metalloproteinases of Treponema pallidum,so as to provide theoretical basis for further study on the role of M23 family metalloproteinases in the pathogenesis of Treponema pallidum.Methods NCBI,CDD,MEROPS,SWISS-MODEL,CDTree,TMHMM,SignalP 4.1,ABCpred were used to analyze the conserved domain,physicochemical properties,transmembrane domain,signal peptide,glycosylation and phosphorylation sites,spatial structure and antigenic epitopes of M23 family metalloproteinases in Treponema pallidum.Results The whole genome sequence of Treponema pallidum contains six M23 family metalloproteinase genes M23-MP1-6.The proteins encoded by M23-M1-6 gene contain HXH domain except M23-MP5.The proteins encoded by M23-MP1-6 gene contain characteristic domain and phosphorylation site of M23 family.M23-MP1,2 and 6 all contain an obvious transmembrane structure.In M23-MP1-6,only M23-MP4 may have a cleavage site between amino acids 17 and 18,and the other proteins do not contain signal peptide.M23-MP1-6 contains B cell epitopes and T cell epitopes.Conclusion Treponema pallidum contains six M23 family metalloproteinase genes M23-MP1-6,which suggests that when Treponema pallidum invades the host,these M23 metalloproteinases may play a role in hydrolyzing elastin to destroy the intercellular connection of the host,change the permeability of blood vessel wall and blood brain barrier,and promote the spread of Treponema pallidum in the host.