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

Date Published: November 20, 2015

Publisher: Public Library of Science

Author(s): Natalia Pakharukova, James A. Garnett, Minna Tuittila, Sari Paavilainen, Mamou Diallo, Yingqi Xu, Steve J. Matthews, Anton V. Zavialov, Joseph D Mougous.

http://doi.org/10.1371/journal.ppat.1005269

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.

Partial Text

All gram-negative bacteria express fibrous adhesive organelles that mediate targeting to sites of infection. The major class of these adhesive pili (or fimbriae) is assembled via the classical, alternative and archaic chaperone-usher (CU) pathways [1]. CU pili are linear polymers made of subunits capable of either self-polymerisation or assembly with other subunits [2,3]. The CU fibre can possess rich binding properties [3–5], which facilitate binding to host cell receptors, as well as mediate biofilm formation through self-association [6] and interactions with abiotic surfaces [7].

Our new structural and biochemical data on the non-classical CU pathway show that, although donor strand complementation governs specific chaperone-subunit and subunit-subunit interactions across all CU families, major differences in how the classical and non-classical pathways implement this mechanism exist.

 

Source:

http://doi.org/10.1371/journal.ppat.1005269

 

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