THE GROE CHAPERONIN MACHINE IS THE MAJOR MODULATOR OF THE CIRCE HEAT-SHOCK REGULON OF BACILLUS-SUBTILIS

Regulation of the heat shock response in bacteria has been studied ext ensively in Escherichia coli where heat shock genes are classified int o three classes and where each class is regulated by a different alter nate sigma factor. Bacillus subtilis serves as a second model bacteriu m to study regulation of the heat shock response in detail. Here, four classes of heat shock genes have been described so far where two are controlled by two different repressor proteins and the third by the al ternate sigma factor sigma(B). Class I heat shock genes consists of tw o operons, the heptacistronic dnaK and the bicistronic groE operon. Tr anscription of the dnaK operon is complex involving two promoters, pre mature termination of transcription, mRNA processing and different sta bilities of the processed transcripts to ensure the appropriate amount s of heat shock proteins under different growth conditions. The transl ation product of the hrcA gene, the first gene of the dnaK operon, bin ds to an operator designated CIRCE element, and its activity is modula ted by the GroE chaperonin system. We assume that the HrcA protein, up on de novo synthesis and upon dissociation from its operator, is prese nt in an inactive form and has to be activated by the GroE chaperonin system resulting in an HrcA-GroE reaction cycle. Induction of class I heat shock genes occurs by the appearance of denatured proteins within the cytoplasm which titrate the GroE system. This results in accumula tion of inactive HrcA repressor and thereby in induction of class I he at shock genes. Upon removal of the non-native proteins from the cytop lasm, the GroE chaperonin will interact with HrcA and promote folding into its active conformation resulting in turning off of class I heat shock genes. This mechanism ensures adequate adjustment of class I hea t shock proteins depending on their actual need.