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

DOI: 10.1371/journal.ppat.1005269 DOI Help
PMID: 26587649 PMID Help

Authors: Natalia Pakharukova (University of Turku) , James Garnett (Imperial College London) , Minna Tuittila (University of Turku) , Sari Paavilainen (University of Turku) , Mamou Diallo (Imperial College London) , Yingqi Xu (Imperial College London) , Steve Matthews (Imperial College London) , Anton V. Zavialov (University of Turku) , Joseph D Mougous (Imperial College London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Plos Pathogens , VOL 11

State: Published (Approved)
Published: November 2015

Open Access Open Access

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.

Subject Areas: Biology and Bio-materials

Instruments: I04-Macromolecular Crystallography