@article{Pakharukova:2015:10.1371/journal.ppat.1005269,
author = {Pakharukova, N and Garnett, JA and Tuittila, M and Paavilainen, S and Diallo, M and Xu, Y and Matthews, SJ and Zavialov, AV},
doi = {10.1371/journal.ppat.1005269},
journal = {PLOS Pathogens},
title = {Structural Insight into Archaic and Alternative Chaperone-Usher Pathways Reveals a Novel Mechanism of Pilus Biogenesis.},
url = {http://dx.doi.org/10.1371/journal.ppat.1005269},
volume = {11},
year = {2015}
}

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TY  - JOUR
AB  - 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.
AU  - Pakharukova,N
AU  - Garnett,JA
AU  - Tuittila,M
AU  - Paavilainen,S
AU  - Diallo,M
AU  - Xu,Y
AU  - Matthews,SJ
AU  - Zavialov,AV
DO  - 10.1371/journal.ppat.1005269
PY  - 2015///
SN  - 1553-7366
TI  - Structural Insight into Archaic and Alternative Chaperone-Usher Pathways Reveals a Novel Mechanism of Pilus Biogenesis.
T2  - PLOS Pathogens
UR  - http://dx.doi.org/10.1371/journal.ppat.1005269
UR  - http://hdl.handle.net/10044/1/27785
VL  - 11
ER  - 

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