PapD-like chaperones provide the missing information for folding of pilin proteins

A fundamental question in molecular biology is how proteins fold into domai ns that can serve as assembly modules for building up large macromolecular structures, The biogenesis of pill on the surface of Gram-negative bacteria requires the orchestration of a complex process that includes protein synt hesis, folding via small chaperones, secretion, and assembly. The results p resented here support the hypothesis that pilus subunit folding and biogene sis proceed via mechanisms termed donor strand complementation and donor st rand exchange. Here we show that the steric information necessary for pilus subunit folding is not contained in one polypeptide sequence. Rather, the missing information is transiently donated by a strand of a small chaperone to allow folding. Providing the missing information for folding, via a 13- amino acid peptide extension to the C-terminal end of a pilus subunit, resu lted in the production of a protein that no longer required the chaperone t o fold. This mechanism of small periplasmic chaperone function described he re deviates from classical hsp60 chaperone-assisted folding.