Conformational Characterization and Classification of Intrinsically Disordered Proteins by Native Mass Spectrometry and Charge‐State Distribution Analysis
Abstract
Intrinsically disordered proteins (IDPs) are systematically under‐represented in structural proteomics studies. Their structural characterization implies description of the dynamic conformational ensembles populated by these polymers in solution, posing major challenges to biophysical methods. “Native” MS (native‐MS) has emerged as a central tool in this field, conjugating the unique MS analytical power with structurally meaningful descriptors, like solvent‐accessible surface area (SASA) and collisional cross section (CCS). This review summarizes recently published papers comparing native‐MS and solution methods, with a focus on charge‐state‐distribution (CSD) analysis for IDP conformational analysis. The results point to substantial agreement, supporting structural interpretation of native‐MS spectra of IDPs. The discussion is integrated with data from our group on “synthetic” IDPs, obtained by reduction and alkylation of natively folded proteins, whose fold is stabilized by disulfide bridges. Finally, an MS‐based compaction index (CI) is introduced, evaluating SASA with reference to globular and fully disorder proteins. Such a parameter can be calculated for single conformers or the whole conformational ensemble, offering a continuous index for IDP comparison and classification.
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Disordered proteins and regions are characterized by broad and heterogeneous ensembles with small differences in relative conformational stabilities and low barriers.
“Disordered proteins (regions) are characterized by broad and heterogeneous ensembles where the differences in the relative conformational stabilities are small, or even minor and the barriers are low.”
From AlphaFold, Artificial Intelligence (AI), and Allostery (2022) · cites this paper as [129]
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- Authors
- Santambrogio, C., Natalello, A., Brocca, S., Ponzini, E., & Grandori, R.
- Affiliations
- University of Milano-Bicocca (IT)
- Corresponding author
- Grandori, Rita
- Venue
- PROTEOMICS
- Publisher
- Wiley
- Published
- 2018-11-29
- Volume
- 19
- Issue
- 6
- Pages
- e1800060-e1800060
- ISSN
- 1615-9853 (ISSN-L)
- 1615-9861
- OpenAlex
- W2898567411
- Cited by
- 51
- References
- 71
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 2 · 2023: 7 · 2022: 12 · 2021: 8 · 2020: 5 · 2019: 5
- FWCI
- 0.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- PROTEOMICS (publishedVersion)
- PubMed (publishedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion)
- Funders
- COST action (BM1403)
- 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
- intrinsically disordered proteins, native mass spectrometry, conformational ensembles, solvent accessible surface area, collision cross sections, compaction index, protein classification
- MeSH terms
- Animals, Humans, Protein Conformation, Protein Folding, Spectrometry, Mass, Electrospray Ionization, Proteomics, Intrinsically Disordered Proteins
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