Aggregation and disaggregation features of the human proteome. Issue 10 (6th October 2020)

• Record Type: Journal Article
• Authors: Määttä, Tomi A; Rettel, Mandy; Sridharan, Sindhuja; Helm, Dominic; Kurzawa, Nils; Stein, Frank; Savitski, Mikhail M
• Is Part Of: Molecular systems biology. Volume 16:Issue 10(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-10-06
• Subjects: aggregation -- disaggregation -- heat shock -- proteomics -- thermal proteome profiling; Molecular biology -- Periodicals; Systems biology -- Periodicals; 572.8
• DOI: 10.15252/msb.20209500
• Languages: English
• ISSNs: 1744-4292

Abstract

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. Synopsis: An in situ proteome‐wide analysis of protein solubility upon heat shock and during recovery reveals protein aggregation and disaggregation features in human cells. Large, hydrophilic and disordered proteins are prone to aggregation. Slow disaggregation is the main strategy for human cells to deal with aggregates. An aggregation‐resistant protein pool exists within aggregating proteins. Abstract : An in situ proteome‐wide analysis of protein solubility upon heat shock and during recovery reveals protein aggregation and disaggregation features in human cells.