Abstract
Ion mobility mass spectrometry (IM-MS) has proven to be an excellent method to characterize the structure of amyloidogenic protein and peptide aggregates, which are formed in coincidence with the development of neurodegenerative diseases. However, it remains a challenge to obtain detailed structural information on all conformational intermediates, originating from the early onset of those pathologies, due to their complex and heterogeneous environment. One way to enhance the insights and the identification of these early stage oligomers is by employing high resolution ion mobility mass spectrometry experiments. This would allow us to enhance the mobility separation and MS characterization. Trapped ion mobility spectrometry (TIMS) is an ion mobility technique known for its inherently high resolution and has successfully been applied to the analysis of protein conformations among others. To obtain conformational information on fragile peptide aggregates, the instrumental parameters of the TIMS-Quadrupole-Time-of-Flight mass spectrometer (TIMS-qToF-MS) have to be optimized to allow the study of intact aggregates and ensure their transmission toward the detector. Here, we investigate the suitability and application of TIMS to probe the aggregation process, targeting the well-characterized M307-N319 peptide segment of the TDP-43 protein, which is involved in the development of amyotrophic lateral sclerosis. By studying the influence of key parameters over the full mass spectrometer, such as source temperature, applied voltages or RFs among others, we demonstrate that by using an optimized instrumental method TIMS can be used to probe peptide aggregation.
Original language | English |
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Pages (from-to) | 193-204 |
Number of pages | 12 |
Journal | Journal of the American Society for Mass Spectrometry |
Volume | 34 |
Issue number | 2 |
Early online date | 12 Jan 2023 |
DOIs | |
Publication status | Published - 1 Feb 2023 |
Bibliographical note
Funding Information:The authors thank Christian Bleiholder (Florida State University); Michael T. Bowers, Xikun Liu, and Veronica Laos (University of California Santa Barbara); Robert L.C Voeten and Melissa Bärenfänger (Vrije Universiteit Amsterdam);and Gábor van Kuijck (Bruker) for their help and insightful discussions. This work is supported by the funding from the research program VICI with project number VI.C.192.024 and Aspasia (015.015.009) from the Dutch Research Council (NWO) awarded to A.M.R. A.D.D. gratefully acknowledges the financial support from the NVMS and ASMS to attend an international conference to receive essential advice from peers about this work.
Publisher Copyright:
© 2023 The Authors. Published by American Chemical Society.