Small heat shock proteins, ClpB and the DnaK system form a functional triade in reversing protein aggregation

Small heat shock proteins (sHsps) can efficiently prevent the aggregation of unfolded proteins in vitro. However, how this in vitro activity translates to function in vivo is poorly understood. We demonstrate that sHsps of Escherichia coli, IbpA and IbpB, co-operate with ClpB and the DnaK system in vitro and in vivo, forming a functional triade of chaperones. IbpA/IbpB and ClpB support independently and co-operatively the DnaK system in reversing protein aggregation. A DeltaibpABDeltaclpB double mutant exhibits strongly increased protein aggregation at 42degreesC compared with the single mutants. sHsp and ClpB function become essential for cell viability at 37degreesC if DnaK levels are reduced. The DnaK requirement for growth is increasingly higher for DeltaibpAB, DeltaclpB, and the double DeltaibpABDeltaclpB mutant cells, establishing the positions of sHsps and ClpB in this chaperone triade.