Figure 1

The process of protein folding in the E. coli cytoplasm. Nascent polypeptides encounter trigger factor (TF) chaperone upon emerging from the ribosomal exit tunnel (1). They can also be captured by DnaK (2) which cooperates with its cofactor DnaJ and nucleotide exchange factor GrpE to promote folding to a native (3) or partially folded conformation. The latter may be re-captured by DnaK (4) and possibly TF to repeat this folding cycle until it reaches its native state, interact with GroEL-GroES (5) to complete folding to its native conformation, or undergo aggregation (6). Upon heat stress, partial unfolding of thermolabile proteins can occur, resulting in exposure of aggregation-prone hydrophobic regions (7). sHsps such as IbpA and IbpB act to "hold" partially unfolded proteins for transfer to Hsp70 and Hsp60 chaperones DnaK and GroEL (8,9), while disaggregation of unfolded proteins is carried out by ClpB in cooperation with the Hsp70 family (10), followed again by their transfer to the DnaK/DnaJ/GrpE machinery for completion of folding.