Escherichia colismall heat shock protein IbpA is an aggregation-sensor that self-regulates its own expression at posttranscriptional levels

Aggregation is an inherent characteristic of proteins. Risk management strategies to reduce aggregation are critical for cells to survive upon stresses that induce aggregation. Cells cope with protein aggregation by utilizing a variety of chaperones, as exemplified by heat-shock proteins (Hsps). The heat stress-induced expression of IbpA and IbpB, small Hsps inEscherichia coli, is regulated by the sigma(32)heat-shock transcriptional regulator and the temperature-dependent translational regulation via mRNA heat fluctuation. We found that, even without heat stress, either the expression of aggregation-prone proteins or theibpAgene deletion profoundly increases the expression of IbpA. Combined with other evidence, we propose novel mechanisms for the regulation of the small Hsps expression. Oligomeric IbpA self-represses theibpA/ibpBtranslation, and mediates its own mRNA degradation, but the self-repression is relieved by sequestration of IbpA into the protein aggregates. Thus, the function of IbpA as a chaperone to form co-aggregates is harnessed as an aggregation sensor to tightly regulate the IbpA level. Since the excessive preemptive supply of IbpA in advance of stress is harmful, the prodigious and rapid expression of IbpA/IbpB on demand is necessary for IbpA to function as a first line of defense against acute protein aggregation.

Automated summary

Cells utilize various chaperones, such as small Hsps like IbpA and IbpB, to combat protein aggregation, with specific regulatory mechanisms in response to heat stress, including self-repression of IbpA and relief of inhibition through sequestration into protein aggregates. These mechanisms help maintain cellular homeostasis under stress conditions.