Abstract
Microorganisms rely on protein interactions to transmit signals, react to stimuli, and grow. One of the best ways to understand these protein interactions is through structural characterization. However, in the past, structural knowledge was limited to stable, high-affinity complexes that could be crystallized. Recent developments in structural biology have revolutionized how protein interactions are characterized. The combination of multiple techniques, known as integrative structural biology, has provided insight into how large protein complexes interact in their native environment. In this mini-review, we describe the past, present, and potential future of integrative structural biology as a tool for characterizing protein interactions in their cellular context.
Highlights
One of the main goals of molecular biology is to understand cellular processes at the molecular level
This is in large part due to recent developments in structural biology, such as the cryo-electron microscopy (cryo-EM) resolution revolution and the increasing accuracy of computational protein structure prediction
When structures from individual proteins are combined with rigorous biochemistry and biophysical experiments, one can begin to build up protein complex structures in a bottom-up integrative structural biology (ISB) approach, whether they are stable or transient (Fig. 4)
Summary
One of the main goals of molecular biology is to understand cellular processes at the molecular level. Any other technique that gives extra information could be integrated with any of the above structural techniques, such as cross-linking mass spectrometry (XL-MS), small angle X-ray scattering (SAXS), small angle neutron scattering (SANS), molecular docking, machine learning generated structural models, protein mutagenesis, or Forster resonance energy transfer (FRET), among many others. Because these techniques have a wide variety of efficiency and resolution, specific combinations of experiments may work better at different structural scales (Fig. 1).
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