Aggregation and disaggregation features of the human proteome
Open accessPublished version of a preprint
Abstract
Protein aggregates have negative implications in disease. While reductionist experiments have increased our understanding of aggregation processes, the systemic view in biological context is still limited. To extend this understanding, we used mass spectrometry‐based proteomics to characterize aggregation and disaggregation in human cells after non‐lethal heat shock. Aggregation‐prone proteins were enriched in nuclear proteins, high proportion of intrinsically disordered regions, high molecular mass, high isoelectric point, and hydrophilic amino acids. During recovery, most aggregating proteins disaggregated with a rate proportional to the aggregation propensity: larger loss in solubility was counteracted by faster disaggregation. High amount of intrinsically disordered regions were associated with faster disaggregation. However, other characteristics enriched in aggregating proteins did not correlate with the disaggregation rates. In addition, we analyzed changes in protein thermal stability after heat shock. Soluble remnants of aggregated proteins were more thermally stable compared with control condition. Therefore, our results provide a rich resource of heat stress‐related protein solubility data and can foster further studies related to protein aggregation diseases.
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- Authors
- Määttä, T. A., Rettel, M., Sridharan, S., Helm, D., Kurzawa, N., Stein, F., & Savitski, M. M.
- Affiliations
- Heidelberg University (DE)
- European Molecular Biology Laboratory (DE)
- Corresponding author
- Savitski, Mikhail M
- ORCID
- Venue
- Molecular Systems Biology
- Published
- 2020-10-01
- Volume
- 16
- Issue
- 10
- Pages
- e9500-e9500
- ISSN
- 1744-4292 (ISSN-L)
- PMC
- PMC7538195
- OpenAlex
- W3092050050
- Cited by
- 34
- References
- 10
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 2 · 2023: 6 · 2022: 8 · 2021: 7 · 2020: 2
- FWCI
- 1.86
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Systems Biology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- European Molecular Biology Laboratory
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
- Keywords
- protein aggregation, protein disaggregation, heat shock, protein solubility, intrinsically disordered regions, aggregation-prone proteins, protein thermal stability, nuclear proteins, protein physicochemical properties, heat stress response, protein aggregation diseases
- MeSH terms
- Cell Line, Cell Nucleus, Cell Survival, Fluorescent Antibody Technique, Histones, Humans, Molecular Weight, Nuclear Proteins, Solubility, Mass Spectrometry, Protein Biosynthesis, Protein Folding, Heat-Shock Response, Proteome
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