Protein structure determination by electron cryo-microscopy

Transmission electron cryo-microscopy (cryoEM) is a versatile tool in the structural analysis of proteins and biological macromolecular assemblies. In this review, we present a brief survey of the methods used in cryoEM, and their current developments. These latest advances provide exciting opportunities for the three-dimensional structural determination of macromolecular complexes that are either too large or too heterogeneous to be investigated by conventional X-ray crystallography or nuclear magnetic resonance (NMR). The endeavour of understanding the function of protein or macromolecular complex is often helped by combining data from electron microscopy and X-ray crystallography. We will thus provide a brief overview of the computational techniques involved in combining data from different techniques for the interpretation of the EM structure.