2D Schematic Free Energy Landscape Illustrating the Effect of Interactions between the Nascent Polypeptide Chain (NC) and Ribosome on the Co-translational Folding Process.
Unfolded (U) and native (N) states are shown folding through a transition state (‡), and the free energy of folding, in the absence of additional interactions, is ΔGfree (indicated by dashed blue lines). However, interactions of unfolded and native states with the ribosome surface to form bound states (UB and NB, respectively) may perturb the effective free energy of folding of the ribosome–nascent chain complex (RNC), ΔGRNC (indicated by dashed red lines). A stronger interaction with the ribosome of the unfolded state relative to the native state is illustrated here (depicted by the lower free energy of UB compared with NB), the effect of which is (i) that the folding equilibrium is shifted from the native state towards the unfolded state, and (ii) that the rates of folding (kf) and unfolding (ku) are both decreased due to the increased free energy barrier heights.