Figure 4.

DnaK directs clients to the native state by binding to the unfolded state and off-pathway misfolded intermediates.A, crystal structure of DnaK SBD bound to model NRLLLTG peptide. B, DnaK employs conformational selection to bind to the unfolded state, but not the native state, driving flux in the pathway toward the native state. C, DnaK can bind to off-pathway intermediates, preventing long-range interactions and increasing the conversion to on-pathway intermediates. DnaK is also able to intervene at multiple other points in the folding landscape, such as at the unfolded state and multiple other nonnative states. Also, there is no “directionality” implied in the action of DnaK on the topological landscape (e.g., DnaK does not know: which direction leads to the native state).