Figure 4.
Evolutionary and Cellular Strategies to Deal with Proteins that Are Likely to Aggregate
Two major solutions to explain how cells are robust to the presence of aggregation-prone proteins have been proposed.
(A) The sequences of such proteins have been subjected to rigorous selection such that they do not easily form aggregates (i.e., avoidance of aggregation is a major evolutionary driving force in the design of protein sequences).
(B) Cellular systems have evolved machineries and mechanisms to either avoid or efficiently clear aggregates.
(C) The results from our integrated analysis provide insights into a third possible solution to this problem. Cellular systems have evolved regulatory strategies that control the availability of aggregation-prone proteins and their encoding transcripts such that they are present for short periods, low quantities, and in precise amounts in a cell. This strategy may ensure that the abundance of aggregation-prone proteins is below the critical concentration.