Pro-sequence-assisted protein folding.

Abstract

Many proteins, including proteases and growth factors, are synthesized as precursors in the form of pre-pro-proteins. Whereas the pre-sequences usually act as signal peptides for transport, the pro-sequences of an increasing number of these proteins have been found to be essential for the correct folding of their associated proteins. In contrast to the action of molecular chaperones, pro-sequences appear to catalyse the protein-folding reaction directly. The similarity between the pro-sequence-assisted folding mechanisms of different proteases supports the hypothesis that a common folding mechanism has developed through convergent evolution. Further, the frequent requirement of the pro-sequences for both folding and intracellular transport or secretion suggests that these two functionalities are intimately related.