Chaperone discovery

Abstract

Molecular chaperones assist de novo protein folding and facilitate the refolding of stress‐denatured proteins. The molecular chaperone concept was coined nearly 35 years ago, and since then, tremendous strides have been made in understanding how these factors support protein folding. Here, we focus on how various chaperone proteins were first identified to play roles in protein folding. Examples are used to illustrate traditional routes of chaperone discovery and point out their advantages and limitations. Recent advances, including the development of folding biosensors and promising methods for the stabilization of proteins in vivo, provide new routes for chaperone discovery. With new methods of chaperone discovery, the question as to whether we have discovered all the chaperones that exist is very pertinent: there may well be important new surprises on the horizon. The image depicts one method of monitoring protein folding, namely the coupling of protein folding to the host stress response. This review cover is the past, present, and future of chaperone discovery.