The Hsp70 chaperone system maintains high concentrations of active proteins and suppresses ATP consumption during heat shock
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Hsp70 chaperones assist protein folding by cycling between the ATP-bound T state with low affinity for substrates and the ADP-bound R state with high affinity for substrates. The transition from the T to R state is catalyzed by the synergistic action of the substrate and DnaJ cochaperones. The reverse transition from the R state to the T state is accelerated by the nucleotide exchange factor GrpE. These two processes, T-to-R and R-to-T conversion, are affected differently by temperature change. Here we modeled Hsp70-mediated protein folding under permanent and transient heat shock based on published experimental data. Our simulation results were in agreement with in vitro wild-type Escherichia coli chaperone experimental data at 25°C and reflected R-to-T ratio dynamics in response to temperature effects. Our simulation results suggested that the chaperone system evolved naturally to maintain the concentration of active protein as high as possible during heat shock, even at the cost of recovered activity after return to optimal growth conditions. They also revealed that the chaperone system evolved to suppress ATP consumption at non-optimal high growing temperatures.
KeywordsGrpE Heat-shock Hsp70 Protein folding Systems biology Temperature
We thank all the members of the E-CELL project at Keio University for their support. This work was supported in part by grants from The 21st Century COE Program “Understanding and Control of Life’s Function via Systems Biology”; from the Leading Project for Biosimulation, Keio University, on behalf of The Ministry of Education, Culture, Sports, Science, and Technology (MEXT, Japan); and from the CREST–JST project “Development of Modeling/Simulation Environments for Systems Biology” on behalf of the Japan Science and Technology Agency.
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