A1 Refereed original research article in a scientific journal
Structural Insight into Archaic and Alternative Chaperone-Usher Pathways Reveals a Novel Mechanism of Pilus Biogenesis
Authors: Pakharukova N, Garnett JA, Tuittila M, Paavilainen S, Diallo M, Xu YQ, Matthews SJ, Zavialov AV
Publisher: PUBLIC LIBRARY SCIENCE
Publication year: 2015
Journal: PLoS Pathogens
Journal name in source: PLOS PATHOGENS
Journal acronym: PLOS PATHOG
Article number: ARTN e1005269
Volume: 11
Issue: 11
Number of pages: 22
ISSN: 1553-7366
eISSN: 1553-7374
DOI: https://doi.org/10.1371/journal.ppat.1005269(external)
Gram-negative pathogens express fibrous adhesive organelles that mediate targeting to sites of infection. The major class of these organelles is assembled via the classical, alternative and archaic chaperone-usher pathways. Although non-classical systems share a wider phylogenetic distribution and are associated with a range of diseases, little is known about their assembly mechanisms. Here we report atomic-resolution insight into the structure and biogenesis of Acinetobacter baumannii Csu and Escherichia coli ECP biofilm-mediating pili. We show that the two non-classical systems are structurally related, but their assembly mechanism is strikingly different from the classical assembly pathway. Non-classical chaperones, unlike their classical counterparts, maintain subunits in a substantially disordered conformational state, akin to a molten globule. This is achieved by a unique binding mechanism involving the register-shifted donor strand complementation and a different subunit carboxylate anchor. The subunit lacks the classical pre-folded initiation site for donor strand exchange, suggesting that recognition of its exposed hydrophobic core starts the assembly process and provides fresh inspiration for the design of inhibitors targeting chaperone-usher systems.
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