Archaic and alternative chaperones preserve pilin folding energy by providing incomplete structural information

J Biol Chem. 2018 Nov 2;293(44):17070-17080. doi: 10.1074/jbc.RA118.004170. Epub 2018 Sep 18.


Adhesive pili are external component of fibrous adhesive organelles and help bacteria attach to biotic or abiotic surfaces. The biogenesis of adhesive pili via the chaperone-usher pathway (CUP) is independent of external energy sources. In the classical CUP, chaperones transport assembly-competent pilins in a folded but expanded conformation. During donor-strand exchange, pilins subsequently collapse, producing a tightly packed hydrophobic core and releasing the necessary free energy to drive fiber formation. Here, we show that pilus biogenesis in non-classical, archaic, and alternative CUPs uses a different source of conformational energy. High-resolution structures of the archaic Csu-pili system from Acinetobacter baumannii revealed that non-classical chaperones employ a short donor strand motif that is insufficient to fully complement the pilin fold. This results in chaperone-bound pilins being trapped in a substantially unfolded intermediate. The exchange of this short motif with the longer donor strand from adjacent pilin provides the full steric information essential for folding, and thereby induces a large unfolded-to-folded conformational transition to drive assembly. Our findings may inform the development of anti-adhesion drugs (pilicides) to combat bacterial infections.

Keywords: Acinetobacter baumannii; Csu pili; X-ray crystallography; adhesive pili; bacterial adhesion; bacterial pathogenesis; biofilm; chaperone; chaperone-usher pathway; fimbriae; nuclear magnetic resonance (NMR); protein folding; protein secretion; protein self-assembly; protein structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter baumannii / chemistry
  • Acinetobacter baumannii / genetics
  • Acinetobacter baumannii / metabolism*
  • Fimbriae Proteins / chemistry*
  • Fimbriae Proteins / genetics
  • Fimbriae Proteins / metabolism
  • Fimbriae, Bacterial / chemistry*
  • Fimbriae, Bacterial / genetics
  • Fimbriae, Bacterial / metabolism
  • Models, Molecular
  • Molecular Chaperones / chemistry
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Protein Folding


  • Molecular Chaperones
  • Fimbriae Proteins

Associated data

  • PDB/5D6H
  • PDB/3F83