Catalysis of protein folding by chaperones in pathogenic bacteria.

Molecular chaperones are thought to inhibit off-pathway interactions such as aggregation from occurring without influencing the on-pathway formation of native structure. Here, we present a mechanism whereby the family of PapD-like chaperones, which are involved in the formation of adhesive pili in pathogenic bacteria, function by suppressing aggregation while simultaneously catalyzing the folding of subunits that make up the pilus. We also show that the Arg-8 residue, invariant in the cleft of all known PapD-like chaperones, makes up part of the active site of the chaperone. The data argue for a temporal mechanism of catalyzed folding. The terminal carboxylate group of a pilus subunit anchors to the active site of the chaperone by hydrogen bonding. This bonding spatially fixes the COOH terminus of the subunit in the correct context for beta-sheet formation, using the edge of the NH(2)-terminal domain of the chaperone as a nucleation site.