1)National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;2)Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
This work was supported by grants from National Science Foundation for Distinguished Young Scholars of China (31925026) and National Key Research and Development Program (2021YFA1301500).
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.
LI Kuan-Ying, WANG Wen-Xue, ZHU Yun, XUE Liang, SUN Fei. Reivew: Frontiers in in situ Cryo-electron Microscopy and Visual Proteomics[J]. Progress in Biochemistry and Biophysics,2024,51(10):2456-2477
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