FIGURE 2.

Protein folding and misfolding dynamics in the cellular environment

Multiple external and internal factors (e.g., molecular and chemical chaperones abundance and activity, ion composition, metabolic state, thermal and oxidative stress) can influence the conformational dynamics of PM proteins by shifting their folding-unfolding equilibrium. The energetically favorable conformers are represented by lower folding free energy (ΔG⁰) of the native polypeptides. Proteotoxic stress- and disease-causing mutations can either thermodynamically and/or kinetically interfere with the folding pathways, as also indicated by the increased ΔG⁰ of partially folded and unfolded conformers.