The application of mass spectrometry (MS) and ion mobility for studying proteins and protein complexes has utility in structural biology and biomedical research. The assessment of protein interactions can address the functional role of proteins and protein complexes. Measuring the molecular masses of protein complexes (i.e., “native” MS) reveals information on stoichiometry of binding and identification of interacting partners. MS and ion mobility measurements can supply information on the structural aspects of protein conformations and supramolecular assemblies in excess of 1 MDa. However, MS can advance an additional layer of information that is critical to structural biology: location (or topology) and dynamics.
Developments in protein MS and tandem MS (MS/MS, or top-down MS) to define the structures of native protein complexes, including the sites of ligand bonding, will be discussed. We are using high resolution Fourier transform ion cyclotron resonance MS to investigate the molecular action of compounds that prevent amyloid fibril formation in neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. Native proteins and complexes are not necessarily static entities, as they are in constant motion and perhaps changing their partners during the “dance” that defines their roles in biological processes. Native MS and top-down MS can be used to decipher the dynamics of protein interactions that govern iron-capture by pathogens. Our work demonstrates the ability of native MS for providing a view of the dynamics of protein-ligand assembly-disassembly that would be difficult to measure by other biophysical methods.
Prof. Ronghu Wu (404-385-1515).