Approaching structural flexibility with flexibility

Three-dimensional electron microscopy (3D-EM) is a powerful technology for imaging macromolecular complexes. Through a process known as singleparticle reconstruction, tens of thousands of separate images of a complex of interest are used to arrive at a single resolved structure. Although this method works sufficiently well for rigid macromolecular complexes, conformationally flexible complexes posed a challenge. Now, Scheres and colleagues describe an algorithm based on maximum-likelihood principles that allows the handling of data from flexible complexes, without any prior knowledge of the structural heterogeneity present in the various copies. They demonstrate the utility of the method for the conformationally heterogeneous Escherichia coli ribosome and simian virus 40 large T-antigen. Brief Communication p27, News & Views p20