Understanding and predicting protein misfolding and aggregation: Insights from proteomics

Area of Science:

• Biochemistry
• Molecular Biology
• Proteomics

Background:

• Protein misfolding and aggregation are implicated in numerous human diseases and aging.
• These aggregation processes can lead to loss of protein function or toxic gain of function.
• Despite potential harm, aggregation is a common property suggesting conserved biological roles.

Purpose of the Study:

• To review how computational and experimental proteomics approaches elucidate protein aggregation mechanisms.
• To understand the cellular, developmental, and evolutionary roles of protein aggregation.
• To decipher organismal strategies for controlling protein aggregation propensities.

Main Methods:

• In vitro studies of individual protein aggregation reactions.
• Large-scale computational analysis of protein sequences.
• Experimental proteomics in model organisms.

Main Results:

• In vitro studies identified structural and sequential determinants of protein aggregation.
• Computational analyses revealed the ubiquity of aggregation-prone sequences and suggested conserved functions.
• Proteomic analyses in model organisms offer global insights into aggregation regulation.

Conclusions:

• Understanding protein aggregation requires global approaches beyond in vitro studies.
• Model organisms and proteomics are crucial for studying aggregation in health and disease.
• Organisms possess evolved strategies to manage the risks associated with protein aggregation.