When one technique is not enough to achieve a complete and accurate 3D structure
To understand protein functioning in the cellular environment, it is essential that researchers determine protein complex assembly and structure beyond that of individual proteins. Solving the structure of large dynamic complexes often requires integrating several complementary techniques, such as biomolecular mass spectrometry (MS) and cryo-electron microscopy (cryo-EM)—an approach known as integrative structural biology.
MS has advanced significantly, impacting the field of structural biology. Technology developments in mass analyzers are at the forefront of driving the growing number of structural biology studies enabled by increased performance in speed, sensitivity, selectivity and a variety of MS fragmentation techniques. Similarly, recent developments in cryo-EM sample preparation, microscope and detector technology, automation in data collection, and image processing make it possible to reproducibly reach near-atomic resolution. Combined, a reliable and complete structure can be solved of macromolecular complexes, including components like protein, post-translational protein modification, DNA, RNA, and lipids.