机构地区:[1]安徽大学生命科学学院生物制药系,安徽大学物质科学与信息技术研究院健康科学与技术研究所,合肥230601
出 处:《中国生物化学与分子生物学报》2022年第3期290-297,共8页Chinese Journal of Biochemistry and Molecular Biology
基 金:国家自然科学基金项目(No.31970103);安徽省重点研究与开发计划面上攻关项目(No.202004a06020035);安徽省自然科学基金(No.2108085MC76)资助。
摘 要:糖基转移酶(glycosyltransferases,GTs)将糖基从活化的供体转移到糖、脂、蛋白质和核酸等受体,其参与的蛋白质糖基化是最重要的翻译后修饰(post-translational modifications,PTMs)之一。近年来越来越多的研究证明,糖基转移酶与致病菌毒力密切相关,在致病菌的黏附、免疫逃逸和定殖等生物学过程中发挥关键作用。目前,已鉴定的糖基转移酶根据其蛋白质三维结构特征分为3种类型GT-A、GT-B和GT-C,其中常见的是GT-A和GT-B型。在致病菌中发挥黏附功能的糖基转移酶,在结构上属于GT-B或GT-C型,对致病菌表面蛋白质(黏附蛋白、自转运蛋白等)进行糖基化修饰,在致病菌黏附、生物被膜的形成和毒力机制发挥具有重要作用。糖基转移酶不仅参与致病菌黏附这一感染初始过程,其中属于GT-A型的一类致病菌糖基转移酶会进入宿主细胞,通过糖基化宿主蛋白质影响宿主信号传导、蛋白翻译和免疫应答等生物学功能。本文就常见致病菌糖基转移酶的结构及其糖基化在致病机制中的作用进行综述,着重介绍了特异性糖基化高分子量(high-molecular-weight,HMW)黏附蛋白的糖基转移酶、针对富丝氨酸重复蛋白(serine-rich repeat proteins,SRRP)糖基化修饰的糖基转移酶、细菌自转运蛋白庚糖基转移酶(bacterial autotransporter heptosyltransferase,BAHT)家族、N-糖基化蛋白质系统和进入宿主细胞发挥毒力作用的大型梭菌细胞毒素、军团菌(Legionella)葡萄糖基转移酶以及肠杆菌科的效应子NleB。为揭示致病菌中糖基转移酶致病机制的系统性研究提供参考,为未来致病菌的诊断、药物设计研发以及疫苗开发等提供科学依据和思路。Glycosyltransferases(GTs)catalyze the transfer of sugar moieties from activated donor molecules to acceptors such as sugars,lipids,proteins,and nucleic acids.Protein glycosylation is one of the most important post-translational modifications(PTMs).In recent years,increasing studies have shown that glycosyltransferases are closely related to the virulence of pathogenic bacteria,and play a key role in adhesion,immune evasion,and host colonization.According to the features of three-dimensional structure,glycosyltransferases are classified into three groups(GT-A,GT-B and GT-C),among which GT-A and GT-B folds are more common.Glycosyltransferases,which play a role in bacterial adhesion,adopt the GT-B or GT-C fold and glycosylate the surface proteins of pathogenic bacteria(adhesion proteins,autotransporters,etc.).It plays an important role in the adhesion of pathogenic bacteria,the formation of biofilm,and the virulence mechanisms.Glycosyltransferases take part in bacterial adhesion process of infection,and glycosyltransferases belonging to GT-A directly glycosylate host proteins and affect host signal transduction,protein translation,and immune response.This review discusses the structure of common pathogenic bacteria glycosyltransferases and the pathogenic mechanisms underlying these diseases of glycosylation.One kind of glycosyltransferases mainly modify their surface proteins,such as the glycosyltransferase for specifically glycosylating high-molecular-weight(HMW)adhesion proteins,glycosyltransferases for glycosylation modification of serine-rich repeat proteins(SRRPs),bacterial autotransporter heptosyltransferase(BAHT)family,and N-linked protein system.The other kinds of glycosyltransferases modulate host responses by directly modifying host proteins,such as Clostridium large cytotoxin,Legionella glycosyltransferase,and the NleB effector from enterobacteria.This review provides a reference for systematically revealing the pathogenic mechanism of glycosyltransferase in pathogenic bacteria,and contributes scientific
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