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Trends Cell Biol. 2016 Nov;26(11):825-837. doi: 10.1016/j.tcb.2016.08.006. Epub 2016 Sep 23.

Cryo-Electron Tomography: Can it Reveal the Molecular Sociology of Cells in Atomic Detail?

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Structural and Computational Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany. Electronic address:
Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, D-82152 Martinsried (Planegg), Germany. Electronic address:


Traditionally, macromolecular structure determination is performed ex situ, that is, with purified materials. But, there are strong incentives to develop approaches to study them in situ in their native functional context. In recent years, cryo-electron tomography (cryo-ET) has emerged as a powerful method for visualizing the molecular organization of unperturbed cellular landscapes with the potential to attain near-atomic resolution. Here, we review recent work on several macromolecular assemblies, demonstrating the power of in situ studies. We also highlight technical challenges and discuss ways to meet them.

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