Integrative Structural Biology of Protein-RNA Complexes

Ribonucleoprotein complexes (RNPs) are central to all processes in the cell. One of the prerequisites to understand how RNPs work is to determine their high-resolution structures. With the recent revolution in cryoelectron microscopy this task has become easier for large RNP machines, such as ribosomes, spliceosomes, and polymerases. However, the transient and highly dynamic nature of many RNPs makes structure determination a challenging task. Thus, an integrative structural and molecular biology approach is required, tackling three key challenges: (1) identification of cognate RNA sequences; (2) collection of structural data by conducting X-ray crystallography, NMR, electron microscopy, small-angle scattering (SAS), and other experiments; and (3) the creation of structural models that integrates all experimental restraints. Given the breadth of expertise required, this review presents an overview of available methods and successful examples with the goal to provide readers with a selection of promising options for structure determination of RNPs.