Structural Insight into Archaic and Alternative Chaperone-Usher Pathways Reveals a Novel Mechanism of Pilus Biogenesis

Natalia Pakharukova, J.A. Garnett, Minna Tuittila, Sari Paavilainen, Mamou Diallo, Yingqi Xu, S.J. Matthews, A.V. Zavialov

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10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere1005269
Number of pages22
JournalPLoS Pathogens
Volume11
Issue number11
DOIs
Publication statusPublished - 2015

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    Pakharukova, N., Garnett, J. A., Tuittila, M., Paavilainen, S., Diallo, M., Xu, Y., Matthews, S. J., & Zavialov, A. V. (2015). Structural Insight into Archaic and Alternative Chaperone-Usher Pathways Reveals a Novel Mechanism of Pilus Biogenesis. PLoS Pathogens, 11(11), [e1005269]. https://doi.org/10.1371/journal.ppat.1005269