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Cyclic Ion Mobility–Collision Activation Experiments Elucidate Protein Behavior in the Gas Phase

Eldrid, C; Ben-Younis, A; Ujma, J; Britt, H; Cragnolini, T; Kalfas, S; Cooper-Shepherd, D; ... Thalassinos, K; + view all (2021) Cyclic Ion Mobility–Collision Activation Experiments Elucidate Protein Behavior in the Gas Phase. Journal of the American Society for Mass Spectrometry 10.1021/jasms.1c00018. (In press). Green open access

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Abstract

Ion mobility coupled to mass spectrometry (IM-MS) is widely used to study protein dynamics and structure in the gas phase. Increasing the energy with which the protein ions are introduced to the IM cell can induce them to unfold, providing information on the comparative energetics of unfolding between different proteoforms. Recently, a high-resolution cyclic IM-mass spectrometer (cIM-MS) was introduced, allowing multiple, consecutive tandem IM experiments (IMn) to be carried out. We describe a tandem IM technique for defining detailed protein unfolding pathways and the dynamics of disordered proteins. The method involves multiple rounds of IM separation and collision activation (CA): IM-CA-IM and CA-IM-CA-IM. Here, we explore its application to studies of a model protein, cytochrome C, and dimeric human islet amyloid polypeptide (hIAPP), a cytotoxic and amyloidogenic peptide involved in type II diabetes. In agreement with prior work using single stage IM-MS, several unfolding events are observed for cytochrome C. IMn-MS experiments also show evidence of interconversion between compact and extended structures. IMn-MS data for hIAPP shows interconversion prior to dissociation, suggesting that the certain conformations have low energy barriers between them and transition between compact and extended forms.

Type: Article
Title: Cyclic Ion Mobility–Collision Activation Experiments Elucidate Protein Behavior in the Gas Phase
Open access status: An open access version is available from UCL Discovery
DOI: 10.1021/jasms.1c00018
Publisher version: https://doi.org/10.1021/jasms.1c00018
Language: English
Additional information: © 2021 American Society for Mass Spectrometry. Published by American Chemical Society. All rights reserved. Available under CC BY licence
Keywords: ion-mobility mass spectrometry; protein unfolding
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10128676
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