Protecting virgin pili

Pili permit uropathogenic Escherichia coli to adhere to, and colonize, host tissues. P pili consist of a rod of PapA subunits connected to a tip fibrillum by a PapK adaptor. Type I pili are also composite structures, with a short tip fibrillum, composed of FimG and the FimH adhesin, joined to a FimA rod. Two parallel studies1xStructural basis of chaperone function and pilus biogenesis. Sauer, F.G. et al. Science. 1999; 285: 1058–1061Crossref | PubMed | Scopus (270)See all References, 2xX-ray structure of the FimC–FimH chaperone–adhesin complex from uropathogenic Escherichia coli. Choudhury, D. et al. Science. 1999; 285: 1061–1066Crossref | PubMed | Scopus (413)See all References published in Science report the crystal structure of complexes between different chaperones and pilin subunits and model the molecular events in pilus biogenesis. They also illustrate how chaperones influence protein folding by protecting virgin (newly made) proteins and preventing non-productive interactions.The pilin-binding domains of both the FimH and PapK subunits have an immunoglobulin (Ig)-like fold composed of antiparallel β strands. In both structures, the final β strand is missing from the Ig fold, leaving a hydrophobic groove exposed on the protein surface. The β strand of the PapD or FimC chaperone fits into the exposed groove on PapK or FimH, respectively, in a process termed ‘donor-strand complementation’, to form a stable water-soluble complex. The protected virgin pilin subunits are then escorted to an usher protein (an oligomeric pore protein in the bacterial outer membrane), which ‘uncaps’ the chaperones and translocates individual pilin subunits across the outer membrane to be added to a growing pilus rod. The amino-terminal strand of each pilin molecule contains a hydrophobic motif that protrudes away from the main body of the chaperone–pilin complex. The hydrophobic motif of a neighbouring pilin subunit takes the place of the β strand of the chaperone and inserts in an anti-parallel fashion into the hydrophobic groove of the virgin pilin. This process of ‘donor-strand exchange’ between subunits with stereochemical complementarity dictates the order of protein assembly, forming a canonical variable-region Ig fold between subunits of the mature pilus.