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Mol Cell. 2015 May 21;58(4):677-89. doi: 10.1016/j.molcel.2015.02.019.

Cryo-EM: A Unique Tool for the Visualization of Macromolecular Complexity.

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Molecular and Cell Biology Department, UC Berkeley, Berkeley, CA 94720-3220, USA; Howard Hughes Medical Institute, UC Berkeley, Berkeley, CA 94720-3220, USA; Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address:
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.


3D cryo-electron microscopy (cryo-EM) is an expanding structural biology technique that has recently undergone a quantum leap progression in its achievable resolution and its applicability to the study of challenging biological systems. Because crystallization is not required, only small amounts of sample are needed, and because images can be classified in a computer, the technique has the potential to deal with compositional and conformational mixtures. Therefore, cryo-EM can be used to investigate complete and fully functional macromolecular complexes in different functional states, providing a richness of biological insight. In this review, we underlie some of the principles behind the cryo-EM methodology of single particle analysis and discuss some recent results of its application to challenging systems of paramount biological importance. We place special emphasis on new methodological developments that are leading to an explosion of new studies, many of which are reaching resolutions that could only be dreamed of just a couple of years ago.

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