Chaperone Action at the Single-Molecule Level

摘要

Natively folded proteins generally have a significant number of hydrophobic residues that cluster together to form a hydrophobic core. However, during the vectorial synthesis on the ribosome and subsequent folding, these hydrophobic residues are exposed. Because folding occurs in a highly crowded environment, exposed residues can lead to undesired interactions that irreversibly harm the folding process. In particular, they can result in the formation of misfolded states and aggregation.~1 There are ample opportunities for such undesired interactions to occur during folding. While secondary structures form on the order of microseconds or faster, folding into the tertiary structure may take up to minutes.~2 In the meanwhile, proteins are diffusing through the highly crowded cellular environment on subsecond time scale.~(3,4) Newly synthesized polypeptides hence can interact with a multitude of cellular components before they gain their native fold. Once properly folded, proteins are at a reduced risk of pathological interactions. However, even when folded, thermodynamic fluctuations in protein structure, especially at elevated temperatures, can induce partial unfolding and misfolding, which in turn increases the probability of unwanted intermolecular interactions.~5