Introduction: Molecular Chaperones and Protein Quality Control

Abstract

Most proteins need to attain and maintain a defined, native three-dimensional structure to carry out their physiological function. In the crowded macromolecular environment of a cell, a specialised and conserved set of machineries called molecular chaperones have evolved to maintain protein homeostasis, or “proteostasis”, and protect the cell from the deleterious accumulation of non-functional and potentially toxic misfolded protein species. In this chapter, we (i) lay out some of the challenges faced during a protein’s lifecycle; (ii) discuss protein aggregation from both biophysical and cellular perspectives; (iii) introduce the major evolutionarily conserved chaperone families; (iv) describe the critical role played by chaperones in protein quality control; (v) highlight mechanisms by which aberrant chaperone levels and function can cause disease; and (vi) pose some outstanding questions and future directions for research in this field.