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bioRxiv · 10.1101/2020.02.05.931675

Aggregation and Disaggregation Features of the Human Proteome

Määttä, T. A.·Rettel, M.·Helm, D.·Stein, F.·Savitski, M. M.
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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 also resulted in 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 to control condition. Our results provide a rich resource of heat stress-related protein solubility data, propose novel roles for intrinsically disordered regions in protein quality control and reveal a protection mechanism to repress protein aggregation in heat stress.

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Määttä, T. A., Rettel, M., Helm, D., Stein, F., Savitski, M. M.. 2020-02-05. Aggregation and Disaggregation Features of the Human Proteome. https://doi.org/10.1101/2020.02.05.931675

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