The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Collision induced unfolding of isolated proteins in the gas phase: past, present, and future
Open accessAbstract
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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“In addition, collision-induced unfolding (CIU), i.e., increasing the internal energy of an ion prior to IM-MS analysis, allows concomitant study of conformational stability, providing more details than IM alone.”
From Higher-order structural characterisation of native proteins and complexes by top-down mass spectrometry (2020) · cites this paper as [26]
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Cites
Lanucara, F., Holman, S. W., Gray, C. J., & Eyers, C. E. (2014) · Nature Chemistry · doi:10.1038/nchem.1889 · Cited by 901 · cited 1×
“charge ratio and reports ion size in terms of an orientationally-averaged collision cross section (CCS), has also been widely deployed in combination with MS as a platform for structural biology [5].”
MethodMembrane proteins bind lipids selectively to modulate their structure and function
Laganowsky, A. D., Reading, E., Allison, T. M., Ulmschneider, M. B., Degiacomi, M. T., Baldwin, A. J., & Robinson, C. V. (2014) · Nature · doi:10.1038/nature13419 · Cited by 804
Evidence for Macromolecular Protein Rings in the Absence of Bulk Water
Ruotolo, B. T., Giles, K., Campuzano, I. D. G., Sandercock, A. M., Bateman, R. H., & Robinson, C. V. (2005) · Science · doi:10.1126/science.1120177 · Cited by 597
Self-citationNaked Protein Conformations: Cytochrome c in the Gas Phase
Clemmer, D. E., Hudgins, R. R., & Jarrold, M. F. (1995) · Journal of the American Chemical Society · doi:10.1021/ja00145a037 · Cited by 493 · cited 3×
“However, as the size and complexity of biomolecules increases, IM-derived CCS values alone often yield insufficient information to define the structures of proteins in detail [7].”
BackgroundMethodProtein Structure in Vacuo: Gas-Phase Conformations of BPTI and Cytochrome c
Shelimov, K. B., Clemmer, D. E., Hudgins, R. R., & Jarrold, M. F. (1997) · Journal of the American Chemical Society · doi:10.1021/ja9619059 · Cited by 415 · cited 2×
“Collisional activation followed by IM-MS has been used to probe the conformations of proteins in the gas phase for nearly two decades [10,11].”
BackgroundMethodPace, C. N., Scholtz, J. M., & Grimsley, G. R. (2014) · FEBS Letters · doi:10.1016/j.febslet.2014.05.006 · Cited by 390 · cited 1×
“One such element is protein stability, often reported as a free energy of protein unfolding and represents one of the most widely utilized descriptors of protein structure [3].”
BackgroundGas-Phase Conformation of Biological Molecules: Bradykinin
Wyttenbach, T., von Helden, G., & Bowers, M. T. (1996) · Journal of the American Chemical Society · doi:10.1021/ja9535928 · Cited by 383 · cited 1×
“Prior to this recent period of expansion, IM-MS was used to primarily assign the conformations of peptides [6] and small proteins [7] in the gas phase.”
MethodKoeniger, S. L., Merenbloom, S. I., Valentine, S. J., Jarrold, M. F., Udseth, H. R., Smith, R. D., & Clemmer, D. E. (2006) · Analytical Chemistry · doi:10.1021/ac051060w · Cited by 275
Hall, Z., Politis, A., Bush, M. F., Smith, L. J., & Robinson, C. V. (2012) · Journal of the American Chemical Society · doi:10.1021/ja2096859 · Cited by 267
Ruotolo, B. T., Hyung, S., Robinson, P. M., Giles, K., Bateman, R. H., & Robinson, C. V. (2007) · Angewandte Chemie International Edition · doi:10.1002/anie.200702161 · Cited by 229
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Ion Activation Methods for Peptides and Proteins
Brodbelt, J. S. (2015) · Analytical Chemistry · doi:10.1021/acs.analchem.5b04563 · Cited by 259
Protein–Small Molecule Interactions in Native Mass Spectrometry
Bennett, J. L., Nguyen, G. T. H., & Donald, W. A. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00293 · Cited by 161
Zhou, M., Lantz, C., Brown, K. A., Ge, Y., Paša-Tolić, L., Loo, J. A., & Lermyte, F. (2020) · Chemical Science · doi:10.1039/d0sc04392c · Cited by 146
Lermyte, F., Tsybin, Y. O., O’Connor, P. B., & Loo, J. A. (2019) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-019-02201-x · Cited by 132
“If this is performed in conjunction with, and prior to, ion mobility measurements, this type of collision-induced unfolding (CIU) experiment can provide valuable insight into (changes in) the stability of various elements of protein structure in the gas phase [17].”
BackgroundNative Mass Spectrometry: Recent Progress and Remaining Challenges
Karch, K. R., Snyder, D. T., Harvey, S. R., & Wysocki, V. H. (2022) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-092721-085421 · Cited by 149
“However, CIU can provide information on the overall conformational landscape and stability of a protein upon ligand binding (33, 45).”
BackgroundMethod
Metadata
- Authors
- Dixit, S. M., Polasky, D. A., & Ruotolo, B. T.
- Affiliations
- University of Michigan (US)
- Corresponding author
- 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)
- 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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