Current Trends in Mass Spectrometry

Biography

Biography: Michał Dadlez

Abstract

The application of mass spectrometry for protein studies extends far beyond classic proteomic analyses in which proteins and their posttranslational modifications are identified and/or quantified. Recent developments of new approaches, like ion mobility separation - IM (providing access to collisional cross section values) or technical improvements in the methods already known (like measurements of the hydrogen-deuterium exchange kinetics) enable efficient application of MS for protein structure studies. These methods allow structural insight into a large group of targets difficult in structure analysis. Among them are oligomerising peptides, including A peptide, main neurotoxic agent in Alzheimer’ s disease, responsible for synaptic dysfunction and neuronal injury. The mechanism of the Aβ peptide self-assembly is still under debate. Using Ion Mobility separation coupled with MS we have measured collisional cross-section values of different oligomeric forms of A, from dimers to hexadecamers. For several oligomers, at least two different forms of different Ω values were detected, indicating the presence of at least two families of conformers: compact and extended. We have also characterized numerous factors shaping the compact/extended species equilibria, like metal binding or point mutations. IM-MS thus detected oligomeric species being both on-pathway in the process of fibril formation, but also alternative structures which may represent potentially most neurotoxic, off-pathway oligomers and allowed their basic structural characterisation in the context of complex mixture of interconverting species.