Aggregation and disaggregation features of the human proteome
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 character...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2020-10-01
|
| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/msb.20209500 |
| _version_ | 1797284959723978752 |
|---|---|
| author | Tomi A Määttä Mandy Rettel Sindhuja Sridharan Dominic Helm Nils Kurzawa Frank Stein Mikhail M Savitski |
| author_facet | Tomi A Määttä Mandy Rettel Sindhuja Sridharan Dominic Helm Nils Kurzawa Frank Stein Mikhail M Savitski |
| author_sort | Tomi A Määttä |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T17:55:18Z |
| format | Article |
| id | doaj.art-ecfe042d0eff49ea8810a14e83ac2c5c |
| institution | Directory Open Access Journal |
| issn | 1744-4292 |
| language | English |
| last_indexed | 2024-03-07T17:55:18Z |
| publishDate | 2020-10-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj.art-ecfe042d0eff49ea8810a14e83ac2c5c2024-03-02T12:42:08ZengSpringer NatureMolecular Systems Biology1744-42922020-10-011610n/an/a10.15252/msb.20209500Aggregation and disaggregation features of the human proteomeTomi A Määttä0Mandy Rettel1Sindhuja Sridharan2Dominic Helm3Nils Kurzawa4Frank Stein5Mikhail M Savitski6Genome Biology Unit European Molecular Biology Laboratory Heidelberg GermanyProteomics Core Facility European Molecular Biology Laboratory Heidelberg GermanyGenome Biology Unit European Molecular Biology Laboratory Heidelberg GermanyProteomics Core Facility European Molecular Biology Laboratory Heidelberg GermanyGenome Biology Unit European Molecular Biology Laboratory Heidelberg GermanyProteomics Core Facility European Molecular Biology Laboratory Heidelberg GermanyGenome Biology Unit European Molecular Biology Laboratory Heidelberg GermanyAbstract 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.https://doi.org/10.15252/msb.20209500aggregationdisaggregationheat shockproteomicsthermal proteome profiling |
| spellingShingle | Tomi A Määttä Mandy Rettel Sindhuja Sridharan Dominic Helm Nils Kurzawa Frank Stein Mikhail M Savitski Aggregation and disaggregation features of the human proteome Molecular Systems Biology aggregation disaggregation heat shock proteomics thermal proteome profiling |
| title | Aggregation and disaggregation features of the human proteome |
| title_full | Aggregation and disaggregation features of the human proteome |
| title_fullStr | Aggregation and disaggregation features of the human proteome |
| title_full_unstemmed | Aggregation and disaggregation features of the human proteome |
| title_short | Aggregation and disaggregation features of the human proteome |
| title_sort | aggregation and disaggregation features of the human proteome |
| topic | aggregation disaggregation heat shock proteomics thermal proteome profiling |
| url | https://doi.org/10.15252/msb.20209500 |
| work_keys_str_mv | AT tomiamaatta aggregationanddisaggregationfeaturesofthehumanproteome AT mandyrettel aggregationanddisaggregationfeaturesofthehumanproteome AT sindhujasridharan aggregationanddisaggregationfeaturesofthehumanproteome AT dominichelm aggregationanddisaggregationfeaturesofthehumanproteome AT nilskurzawa aggregationanddisaggregationfeaturesofthehumanproteome AT frankstein aggregationanddisaggregationfeaturesofthehumanproteome AT mikhailmsavitski aggregationanddisaggregationfeaturesofthehumanproteome |