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Biol Cell. 2017 Feb;109(2):81-93. doi: 10.1111/boc.201600042. Epub 2016 Nov 25.

The integrative role of cryo electron microscopy in molecular and cellular structural biology.

Orlov I1,2,3,4, Myasnikov AG1,2,3,4, Andronov L1,2,3,4, Natchiar SK1,2,3,4, Khatter H1,2,3,4, Beinsteiner B1,2,3,4, Ménétret JF1,2,3,4, Hazemann I1,2,3,4, Mohideen K1,2,3,4, Tazibt K1,2,3,4, Tabaroni R1,2,3,4, Kratzat H1,2,3,4, Djabeur N1,2,3,4, Bruxelles T1,2,3,4, Raivoniaina F1,2,3,4, Pompeo LD1,2,3,4, Torchy M1,2,3,4, Billas I1,2,3,4, Urzhumtsev A1,2,3,4, Klaholz BP1,2,3,4.

Author information

Centre for Integrative Biology (CBI), Department of Integrated Structural Biology, IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Illkirch, France.
Centre National de la Recherche Scientifique (CNRS) UMR 7104, Illkirch, France.
Institut National de la Santé et de la Recherche Médicale (INSERM) U964, Illkirch, France.
Université de Strasbourg, Strasbourg, France.


After gradually moving away from preparation methods prone to artefacts such as plastic embedding and negative staining for cell sections and single particles, the field of cryo electron microscopy (cryo-EM) is now heading off at unprecedented speed towards high-resolution analysis of biological objects of various sizes. This 'revolution in resolution' is happening largely thanks to new developments of new-generation cameras used for recording the images in the cryo electron microscope which have much increased sensitivity being based on complementary metal oxide semiconductor devices. Combined with advanced image processing and 3D reconstruction, the cryo-EM analysis of nucleoprotein complexes can provide unprecedented insights at molecular and atomic levels and address regulatory mechanisms in the cell. These advances reinforce the integrative role of cryo-EM in synergy with other methods such as X-ray crystallography, fluorescence imaging or focussed-ion beam milling as exemplified here by some recent studies from our laboratory on ribosomes, viruses, chromatin and nuclear receptors. Such multi-scale and multi-resolution approaches allow integrating molecular and cellular levels when applied to purified or in situ macromolecular complexes, thus illustrating the trend of the field towards cellular structural biology.


Crystallography; Structural biology; Super-resolution microscopy; cryo electron microscopy; cryo electron tomography

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