内源性蛋白质交联的生物质谱分析进展  

Mass spectrometry-based endogenous protein crosslinking omics

作　　者：韦秋实 宫鹏云 李诺敏 刘超[2] 张永谦[1] 邓玉林[1] Qiushi Wei;Pengyun Gong;Nuomin Li;Chao Liu;Yongqian Zhang;Yulin Deng(School of Life Science,Beijing Institute of Technology,Beijing 100081,China;Advanced Innovation Center for Big Data-Based Precision Medicine,Beihang University,Beijing 100191,China;Institute of Engineering Medicine,Beijing Institute of Technology,Beijing 100081,China)

机构地区：[1]北京理工大学生命学院,北京100081 [2]北京航空航天大学大数据精准医疗高精尖创新中心,北京100191 [3]北京理工大学医工融合研究院,北京100081

出　　处：《科学通报》2021年第36期4633-4648,共16页Chinese Science Bulletin

基　　金：北京理工大学科技创新计划前沿交叉与学科创新专项计划(2021CX11017)资助。

摘　　要：内源性蛋白质交联通常指细胞内蛋白质分子间或蛋白质分子内中的两个氨基酸被肽键之外的共价键相连,其形成会对蛋白质构象和功能造成影响.质谱具有高通量、高灵敏度等特点,是大规模鉴定内源性蛋白质交联的工具之一.结合质谱在组学水平上对内源性蛋白质交联的研究工作层出不穷,但在样品处理、数据采集、定性分析、定量分析和生信分析等环节还有诸多问题仍待解决,构建一套完整的内源性蛋白质交联技术体系将极大推动交联组学研究的开展.因此,本文对内源性蛋白质交联相关研究工作进行了概述,总结了目前内源性蛋白质交联研究中取得的重要成果,梳理了基于质谱的内源性蛋白质交联分析工作流程,最后对内源性蛋白质交联在组学水平上的发展提出了展望.Endogenous protein crosslinking usually means the connection of two amino acids in one or two proteins by covalent bonds,which includes intermolecular and intramolecular crosslinks.As a special posttranslational modification of proteins,endogenous protein crosslinking affects the structure and function of the proteins.The main endogenous protein crosslinks currently discovered in prokaryotes and eukaryotes are disulfide bonds,isopeptide bonds,ditryptophan,dityrosine,formaldehyde,methylglyoxal,NOS bridges and so on.All these crosslinks have been shown to have important effects on biological processes and molecular functions.The formation of endogenous protein crosslinking comprises the enzymecatalyzed and non-enzyme-catalyzed.It is reported that several enzymes are utilized to crosslink the proteins in the literature,such as protein disulfide isomerase,transglutaminase,sortase A,tyrosinase,laccase and peroxidase.Some enzymes are already applied for protein crosslinking in the field of the food industry.However,the endogenous substrates of these enzymes are not fully discovered in vivo so far.In addition,the mechanism of protein crosslinks and the function of crosslink protein require further exploration.Mass spectrometry is a high-throughput and high-sensitivity tool that is reliable for the large-scale identification of endogenous protein crosslinking.In recent years,there have been an everincreasing number of studies on endogenous protein crosslinking by mass spectrometry at the omics level,and mass spectrometry has become one important tool to study the endogenous protein crosslinking.For example,it is reported that for the first time,199 disulfide bonds are identified in Escherichia coli and 568 disulfide bonds are identified in secreted proteins of endothelial cells.The results show that disulfide bonds can be divided into two categories:structural and allosteric disulfide bonds.Allosteric disulfide bonds are involved in catalysis and regulation in the cell.Besides the disulfide bond,other types of endogenous

关 键 词：内源性交联组学 生物质谱 分子内交联 分子间交联 

分 类 号：Q811.4[生物学—生物工程]