Cryo-electron microscopy and single-particle 3D image reconstruction techniques have been used to examine a broad spectrum of samples ranging from 500 kDa protein complexes to large subcellular organelles. The attainable resolution has improved rapidly over the past few years. Structures of both symmetric and asymmetric assemblies at approximately 7.5 A have been reported. Together with X-ray crystallography, three-dimensional cryo-electron microscopy reconstruction has provided important insights into the function of many biological systems in their native biochemical contexts.
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We sincerely thank Karin M Reinisch, Timothy S Baker, Michael G Rossmann, Stephen C Harrison and Qing R Fan for their helpful comments on the manuscript. We thank Yu Chen for his help with Fig. 1 . This manuscript is supported by National Institutes of Health grant number GM33050 to Timothy S Baker. W Zhang is a recipient of the Purdue Research Foundation fellowship.