Understanding macromolecular structure and dynamics of biological complexes such as protein-protein, protein-ligand and antibody-antigen are of great biological importance. These interactions are governed, in part, by residues located on the surface of the interacting proteins, which will here forth be referred to as solvent-accessible. Nuclear Magnetic Resonance (NMR), and crystallographic methods are the foundation of rapid progress in this area. Many biological questions of interest invoke questions of protein dynamics, ligand binding, complex formation, or the structural effects of post-translational modifications. Many of these experiments are beyond the range of classical structural biology approaches and structural mass spectrometry (MS) methods have been very successful in filling this technology gap. The fundamental contributions of MS to structural biology studies have grown dramatically due to increases in instrument sensitivity and resolution that have accrued over the past 15 years. This has advanced our ability to reliably sequence and identify protein fragments and their modified products, a feature on which structural mass spectrometry fundamentally relies.
X-Ray Footprinting MS
- Can accommodate membrane proteins
- Good for macromolecular assemblies that cannot be crystallized or are too big for NMR
- Provides information about interactions of bulk proteins, bound proteins and how water orders itself
- Provide protein and water dynamics information
- Need purified protein
Kiselar J, Chance MR.
Annu Rev Biophys. 2018 Mar 14. doi: 10.1146/annurev-biophys-070317-033123.