3A-PL-1420 PDF
The Potential Role of Native Protein Mass Spectrometry in an Integrative Structural Biology Approach
Advanced mass spectrometry (MS) has capabilities to offer structural biologists layers of insight into the details of protein complexes. Mass measurements deliver information on stoichiometry of binding partners directly, even for multi-ligand hetero-complexes and molecular machines with masses well beyond 1 MDa. ESI-MS can measure proteins and complexes from aqueous solution at near neutral pH, i.e., “native" MS. Further, “top-down" mass spectrometry of protein complexes can be applied to probe ligand-binding sites and yield topological information of large complexes.
Recent data using high resolution Fourier transform ion cyclotron resonance (FT-ICR) MS will be shown to provide examples of the capabilities of native MS and top-down MS. We are using electron capture dissociation (ECD)/FT-ICR 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 top-down MS generates information on the surface topology of protein complexes to 800 kDa. We aim to relate the architecture of the gas phase protein to the solution phase state as a means to further develop MS for structural biology. Native MS should be one of several approaches to provide important data for an integrated approach to structural biology.