Gas Phase Stability of Protein Ions in a Cyclic Ion Mobility Spectrometry Traveling Wave Device.

Abstract

Ion mobility mass spectrometry (IM-MS) allows separation of native protein ions into "conformational families". Increasing the IM resolving power should allow finer structural information to be obtained and can be achieved by increasing the length of the IM separator. This, however, increases the time that protein ions spend in the gas phase and previous experiments have shown that the initial conformations of small proteins can be lost within tens of milliseconds. Here, we report on investigations of protein ion stability using a multipass traveling wave (TW) cyclic IM (cIM) device. Using this device, minimal structural changes were observed for Cytochrome C after hundreds of milliseconds, while no changes were observed for a larger multimeric complex (Concanavalin A). The geometry of the instrument (Q-cIM-ToF) also enables complex tandem IM experiments to be performed, which were used to obtain more detailed collision-induced unfolding pathways for Cytochrome C. The instrument geometry provides unique capabilities with the potential to expand the field of protein analysis via IM-MS.

Anal Chem. 2019 Jun 5. doi: 10.1021/acs.analchem.8b05641. [Epub ahead of print]
Eldrid C(1), Ujma J(2), Kalfas S(1), Tomczyk N(1), Giles K(2), Morris M(2), Thalassinos K(1,3)
1 - Institute of Structural and Molecular Biology, Division of Biosciences , University College London , London , WC1E 6BT , United Kingdom.
2 - Waters Corporation , Wilmslow , SK9 4AX , United Kingdom.
3 - Institute of Structural and Molecular Biology, Birkbeck College , University of London , London , WC1E 7HX , United Kingdom.

PMID: 31117399 DOI: 10.1021/acs.analchem.8b05641