Frontiers in in situ Cryo-electron Microscopy and Visual Proteomics
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.
structural biologycell biologysystems biologycryo-electron microscopycryo-electron tomographyvisual proteomicssub-tomogram averagingcryo-correlative light and electron microscopyartificial intelligence