Info box 1: Integrative structural biology

Integrative structural biology refers to the determination of structural model of a protein or protein complex using a variety of different structural methods, typically X-ray crystallography, nuclear magnetic resonance spectrometry (NMR), single-particle electron cryo-microscopy (cryoEM) and small-angle X-ray scattering [12, 13]. Traditionally, this has meant the fitting of high-resolution crystal structures into nanometer resolution cryoEM maps to generate an atomic model for a larger protein complex. Recent technological and computational developments are pushing these boundaries, and current methods such as chromatographic co-purification of protein complexes, cross-linking and hydrogen–deuterium exchange mass spectrometry, light scattering, mutagenesis and molecular modeling are adding valuable information for data interpretation [12, 14]. The individual pieces of data gathered using the different methods provide valuable restraints for the determination of the conformation(s), position and orientation of the components. The simultaneous use of such restraints can significantly improve the accuracy, precision and completeness of a given protein complex model [12].