Molecular chaperones and their denaturing effect on client proteins

Advanced NMR methods combined with biophysical techniques have recently provided unprecedented insight into structure and dynamics of molecular chaperones and their interaction with client proteins. These studies showed that several molecular chaperones are able to dissolve aggregation-prone polypeptides in aqueous solution. Furthermore, chaperone-bound clients often feature fluid-like backbone dynamics and chaperones have a denaturing effect on clients. Interestingly, these effects that chaperones have on client proteins resemble the effects of known chaotropic substances. Following this analogy, chaotropicity could be a fruitful concept to describe, quantify and rationalize molecular chaperone function. In addition, the observations raise the possibility that at least some molecular chaperones might share functional similarities with chaotropes. We discuss these concepts and outline future research in this direction.

Automated summary

Advanced NMR methods combined with biophysical techniques have provided new insights into the structure and dynamics of molecular chaperones and their interactions with client proteins. These studies suggest that molecular chaperones can dissolve aggregation-prone polypeptides and denature client proteins, similar to the effects of chaotropic substances. The concept of chaotropicity may be useful in describing and quantifying the function of molecular chaperones and potentially identifying functional similarities with chaotropes.