Aggregation and disaggregation features of the human proteome.

Area of Science:

• Cellular Biology
• Proteomics
• Biochemistry

Background:

• Protein aggregates are implicated in various diseases.
• Understanding protein aggregation in a cellular context remains limited.
• Reductionist studies offer insights but lack systemic biological views.

Purpose of the Study:

• To characterize protein aggregation and disaggregation in human cells post-heat shock.
• To identify characteristics of aggregation-prone proteins.
• To investigate the relationship between protein properties and disaggregation rates.

Main Methods:

• Mass spectrometry-based proteomics was employed.
• Human cells were subjected to non-lethal heat shock.
• Protein aggregation, disaggregation, and thermal stability were analyzed.

Main Results:

• Aggregation-prone proteins were enriched in nuclear proteins with intrinsically disordered regions, high molecular mass, high isoelectric point, and hydrophilicity.
• Most aggregated proteins disaggregated during recovery, with rates inversely proportional to aggregation propensity.
• Intrinsically disordered regions correlated with faster disaggregation, but other characteristics did not.
• Soluble remnants of aggregated proteins exhibited increased thermal stability.

Conclusions:

• Heat shock induces aggregation of specific protein types in human cells.
• Protein disaggregation is a regulated process influenced by aggregation propensity and intrinsically disordered regions.
• The findings provide valuable data on heat stress-induced protein solubility and aggregation, aiding research into related diseases.