原位冷冻电镜技术和可视蛋白质组学前沿  

Frontiers in in situ Cryo-electron Microscopy and Visual Proteomics

作　　者：李宽莹 王闻雪 朱赟 薛亮 孙飞[1,2] LI Kuan-Ying;WANG Wen-Xue;ZHU Yun;XUE Liang;SUN Fei(National Laboratory of Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China;Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou 510530,China)

机构地区：[1]中国科学院生物物理研究所生物大分子国家重点实验室,北京100101 [2]中国科学院广州生物医药与健康研究院,广州510530

出　　处：《生物化学与生物物理进展》2024年第10期2456-2477,共22页Progress In Biochemistry and Biophysics

基　　金：国家杰出青年科学基金(31925026);国家重点研发计划(2021YFA1301500)资助项目。

摘　　要：近年来,随着原位冷冻电镜技术和人工智能技术的不断发展,结构生物学的研究模式发生了重大转变。结构解析不再局限于分离提纯的单一生物大分子,而是在细胞甚至组织内原位直接解析生物大分子的高分辨率结构,并对亚细胞区域整体分子景观进行结构探索,从而更深刻地理解细胞与组织内生命活动的分子机制。通过展示细胞内不同蛋白质复合物的精细原位结构,可以进一步生成蛋白质组的可视化定量空间分子结构功能图谱,即可视蛋白质组学。以原位冷冻电镜技术为代表的新技术能够在空间水平阐明细胞内蛋白质组的三维相互作用网络,促进从整体上系统性地理解细胞内生物大分子结构功能与互作机制。为推动中国原位冷冻电镜技术和可视蛋白质组学的发展,本文总结了其研究模式和最新前沿进展,结合具体实例展示了新概念与新技术的先进性,并对发展前景进行了展望。In recent years,with the continuous development of in situ cryo-electron microscopy(cryo-EM)and artificial intelligence(AI)technologies,the research of structural biology has undergone a paradigm shift.Structural analysis is no longer confined to isolated and purified biomolecules,and determination of high-resolution in situ structures directly within cells and tissues becomes feasible.Furthermore,structural analysis of the molecular landscapes of subcellular regions can be performed to gain a deeper understanding of the molecular mechanisms of living activities in the native functional context.Through determining in situ structures of various protein complexes within the cell,it is feasible to visualize the proteome with spatial and quantitative information,which is often referred to as visual proteomics.Emerging in situ structural methods represented by cryo-electron tomography(cryo-ET)hold the promise to elucidate the three-dimensional interaction networks of the intracellular proteome and understand their activities in a systematic manner.To advance in situ cryo-EM/ET and visual proteomics in China,this review summarizes the new research paradigms and technological advances,showcases the superiority of new concepts and technologies with representative examples,and discusses the future prospects in the field.

关 键 词：结构生物学 细胞生物学 系统生物学 冷冻电镜 冷冻电子断层成像 可视蛋白质组学 子断层结构分析 冷冻光电关联 人工智能 

分 类 号：Q6-3[生物学—生物物理学]