PROTEOMICS 2016* Structural characterisation of biomolecular assemblies by ion mobility-mass spectrometry (#041)
A precise network of interacting biomolecules, including proteins, DNA and lipids, allow for the function and control of all biological processes. Consequently, to understand these processes and offer potential for intervention, for example in the treatment of human disease, it is useful to have an understanding of the molecular components and their binding interactions. However, structural characterisation of such complex, heterogeneous and dynamic systems remains a challenge, in part due to analytical limitations of current structural biology approaches.
Ion-mobility mass-spectrometry (IM-MS) has emerged as a complementary tool for biomolecule structure determination, and in some cases a structural biology method in its own right. It is capable of defining identity, stoichiometry, size, structural arrangement and subunit interactions in a biomolecular assembly in a single experiment.
Here will be discussed recent advances in IM-MS methodology, and our application of native IM-MS and chemical cross-linking methods, in combination with complementary biophysical methods, to offer new insight into biological assemblies. We have applied these methods to assemblies of interest in human disease, for example; characterising the protein-protein and protein-lipid interactions mediating misfolding and toxicity in amyloid diseases such as Parkinson’s and Alzheimer’s Disease.
