Disulfide bonds: Protein folding and subcellular protein trafficking

Abstract

The study of disulfide-bond-containing proteins has advanced our understanding of the mechanism(s) by which the majority of secretory and membrane-bound proteins acquire their biologically functional folded forms. This covalent linkage has been exploited by a number of research laboratories to harness or trap intermediates populating the folding trajectories of biopolymers. The resulting body of gathered in vitro data demonstrates that, in general, there is a common event underscoring the maturation of disulfide- bond-containing proteins. This commonality is the existence of competition between a physical, conformational folding reaction and a chemical, thiol-disulfide exchange reaction during fold acquisition. The competition, in turn, impacts the fate of the polypeptide in being secreted or retrotranslocated. The role of a host of subcellular factors, including protein disulfide isomerase, that influences this critical spatiotemporal juncture of the foldmaturation process is discussed. Finally, the impact of this competition on the onset of neurodegenerative disorders is elaborated upon. © 2012 The Author Journal compilation © 2012 FEBS.