New Directions for Vectorial Protein Folding

Abstract

In vivo, protein folding typically proceeds vectorially, from one end of the polypeptide chain to the other. N- to C-terminal vectorial folding occurs during polypeptide chain synthesis by the ribosome, and transport of unfolded polypeptides through the Sec translocon. C- to N-terminal vectorial folding, while less common, occurs during the maturation of some classes of secreted proteins. For example, members of the autotransporter (AT) family of virulence proteins from Gram-negative bacteria are first secreted across the bacterial inner membrane from N- to C-terminus, and then across the outer membrane from C- to N-terminus. Here we demonstrate that these different folding vectors significantly alter the folding mechanism for pertactin, an archetypal AT protein. Moreover, it is now clear that pertactin and other AT proteins exploit these different folding mechanisms to increase secretion efficiency.