使用电子断层技术对IgG1抗体逐个分子的三维重构与结构分析  

3D Reconstruction and Structural Study of IgG1 Antibody by Individual-particle Electron Tomography

作　　者：张星[1,2] 廖雨恒 童慧敏 张磊[1] 张胜利[1] 任罡 

机构地区：[1]西安交通大学理学院应用物理系,西安710049 [2]The Molecular Foundry,Lawrence Berkeley National Laboratory

出　　处：《生物化学与生物物理进展》2016年第9期839-849,共11页Progress In Biochemistry and Biophysics

基　　金：美国能源部基础科学基金(DE-AC02-05CH11231);美国国立卫生研究院(NIH)基金(NHLBI;#1R01HL115153);中国国家自然科学基金(11374237;11504287)资助项目~~

摘　　要：抗体(antibody)又称免疫球蛋白(immunoglobulin,Ig),是人体免疫反应的重要参与者.了解抗体的结构和结构动态特征,是理解人体免疫作用机理、修复或提高免疫能力、定向设计抗体以治疗各种疾病的基础.本文以人体IgG1抗体为对象,综述了使用透射电子显微学方法研究IgG1抗体结构方向的最新进展.详细介绍了使用逐个分子的电子断层三维重构技术(individual-particle electron tomography,IPET)对抗体进行结构研究的方法,包括样品制备、图像处理和数据分析等.并描述了利用该技术,在研究抗体结合肽分子后的结构形变和通过收集不同构象来研究抗体动态结构特征方面所取得的阶段性成果.最后,对尚待解决的关键问题与该技术未来的发展方向进行了讨论与展望.Antibody（also named as an immunoglobulin, Ig）, a most important macromolecule for immune response in human body, has been developed as macromolecular drug to treat the cancer and immune diseases.Understanding of antibody three-dimensional（3D） structure and fluctuation could be an important step for further understanding and controlling the antibody pharmacological function. However, the study is limited by antibody flexible structure. In this paper, we reviewed the current research progresses on structural study of human IgG1 antibody conducted by our recently developed individual-particle electron tomography（IPET） method. The review includes the sample preparation method, basic logic of image processing strategy, 3D analysis and its application in antibody-drug conjunction and antibody structural fluctuation. We also discussed the strengths and weakness of the technique.

关 键 词：抗体 免疫球蛋白 透射电子显微学 电子断层三维重构技术 

分 类 号：O469[理学—凝聚态物理] Q-33[理学—电子物理学]