Cited by 235Mass Spectrometry Techniques and ApplicationsProtein Structure and DynamicsAdvanced Proteomics Techniques and Applications

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Collision induced unfolding of isolated proteins in the gas phase: past, present, and future

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Dixit, Sugyan M, Polasky, Daniel A, Ruotolo, Brandon T·2018·Current Opinion in Chemical Biology

DOI 10.1016/j.cbpa.2017.11.010PMC PMC5828980

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Abstract

Rapidly characterizing the three-dimensional structures of proteins and the multimeric machines they form remains one of the great challenges facing modern biological and medical sciences. Ion mobility-mass spectrometry based techniques are playing an expanding role in characterizing these functional complexes, especially in drug discovery and development workflows. Despite this expansion, ion mobility-mass spectrometry faces many challenges, especially in the context of detecting small differences in protein tertiary structure that bear functional consequences. Collision induced unfolding is an ion mobility-mass spectrometry method that enables the rapid differentiation of subtly-different protein isoforms based on their unfolding patterns and stabilities. In this review, we summarize the modern implementation of such gas-phase unfolding experiments and provide an overview of recent developments in both methods and applications.

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The power of ion mobility-mass spectrometry for structural characterization and the study of conformational dynamics
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Method
Membrane proteins bind lipids selectively to modulate their structure and function
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Self-citation
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BackgroundMethod
Protein Structure in Vacuo: Gas-Phase Conformations of BPTI and Cytochrome c
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BackgroundMethod
Forces stabilizing proteins
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Background
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Method
An IMS−IMS Analogue of MS−MS
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Self-citation

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Background
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Background
Ion Activation Methods for Peptides and Proteins
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Self-citation
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Method
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Background
Direct characterization of overproduced proteins by native mass spectrometry
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Self-citation
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“In an effort to assess antibody structures in greater detail, collision induced unfolding (CIU) experiments can be performed.(29) This technology involves the collisional activation of protein ions prior to IM-MS separation in order to initiate protein unfolding events in the gas-phase.”
MethodSelf-citation
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Self-citation
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Background
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Method
Ion mobility–mass spectrometry reveals the role of peripheral myelin protein dimers in peripheral neuropathy
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Self-citation
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Background
Enhanced oligomerization of full-length RAGE by synergy of the interaction of its domains
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Method
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Self-citation
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“Particularly for proteins, the term ‘collisioninduced unfolding’ was coined to describe this behaviour similar to denaturation 1 .”
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Background
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“CIU has been used to distinguish between modes of ATP-competitive kinase inhibitors [25], in biosimilar analysis [26, 27], to assess biotherapeutics [28], and to probe the binding of specific lipids to membrane protein complexes [29–33].”
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Authors: Dixit, S. M., Polasky, D. A., & Ruotolo, B. T.
Affiliations: University of Michigan (US)
Corresponding author: Ruotolo, Brandon T
ORCID: Dixit, Sugyan M
Polasky, Daniel A
Ruotolo, Brandon T
Venue: Current Opinion in Chemical Biology
Publisher: Elsevier BV
Published: 2018-02
Volume: 42
Pages: 93-100
ISSN: 1367-5931 (ISSN-L)
DOI: 10.1016/j.cbpa.2017.11.010
PMC: PMC5828980
OpenAlex: W2772936471
Cited by: 235
References: 48
Citations by year: 2026: 21 · 2025: 24 · 2024: 35 · 2023: 28 · 2022: 24 · 2021: 35 · 2020: 31 · 2019: 26 · 2018: 10
FWCI: 2.11
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (am, 307 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Current Opinion in Chemical Biology (acceptedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Science Foundation (1253384)
National Institutes of Health
NIGMS (R01 GM095832)
Eli Lilly and Company
Agilent Technologies
Topics: Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
Keywords: collision-induced unfolding, ion mobility mass spectrometry, protein tertiary structure, protein isoforms, protein stability, protein complexes, drug discovery
MeSH terms: Ion Mobility Spectrometry, Biological Products, Gases, Protein Conformation, Proteins, Mass Spectrometry, Protein Structure, Secondary, Protein Isoforms, Drug Discovery, High-Throughput Screening Assays, Protein Unfolding

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Collision induced unfolding of isolated proteins in the gas phase: past, present, and future

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