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



: Pakharukova N, McKenna S, Tuittila M, Paavilainen S, Malmi H, Xu Y, Parilova O, Matthews S, Zavialov AV

Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

: 2018

: Journal of Biological Chemistry

: The Journal of biological chemistry

: J Biol Chem

: 293

: 44

: 17070

: 17080

: 11

: 0021-9258

: 1083-351X

DOI: https://doi.org/10.1074/jbc.RA118.004170

: https://research.utu.fi/converis/portal/detail/Publication/36435333


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.

Last updated on 2024-26-11 at 21:18