Dr. Stephan Witt's Research Images

Schematic of protein synthesis, folding and misfolding, and aggregation in an E. coli cell. Recent genetic and biochemical experiments have revealed that DnaK/DnaJ/GrpE function co-translationally in cooperation with ribosome-bound trigger factor, which is a prolyl isomerase (1). An essential post-translational function of DnaK is to break up large protein aggregates, and DnaK accomplishes this in concert with the Hsp104 chaperone ClpB (2). TF, K, J, and E denote trigger factor, DnaK, DnaJ, and GrpE, respectively. I denotes a productive folding intermediate. The concentration of the free unfolded protein in a cell is vanishingly small. Misfolded and aggregated proteins, which can persist in cells for very long times, can be potentially very toxic to cells.

1. Deuerling, E., Schulze-Specking, A., Tomoyasu, T., Mogk, A., and Bukau, B. (1999) Nature 400, 693-6.
2. Goloubinoff, P., Mogk, A., Zvi, A. P., Tomoyasu, T., and Bukau, B. (1999) Proc Natl Acad Sci U S A 96, 13732-7.

A. The domain structure of DnaK. B. Structure of the N-terminal ATPase domain of DnaK. DnaK contains only one tryptophan residue, located at position 102, which is shown in blue. The image was created using the Brookhaven PDB data file 1DKG. C. Structure of the C-terminal polypeptide-binding domain of DnaK with a bound NR peptide (NRLLLTG), shown in purple. The two residues that comprise the hydrophobic arch (Met404 and Ala429) are shown in green. Residues that comprise the latch between the b-sandwich and lid are shown in red. The five helices that constitute the lid are marked A - E. The image was created using the Brookhaven PDB data file 1DKX.

Complex between the ATPase domain of DnaK and a GrpE homodimer (Harrison et al. Science [1997] 276:431-435).