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

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 a...

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Autores principales: Pakharukova, Natalia, Garnett, James A., Tuittila, Minna, Paavilainen, Sari, Diallo, Mamou, Xu, Yingqi, Matthews, Steve J., Zavialov, Anton V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4654587/
https://www.ncbi.nlm.nih.gov/pubmed/26587649
http://dx.doi.org/10.1371/journal.ppat.1005269
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author Pakharukova, Natalia
Garnett, James A.
Tuittila, Minna
Paavilainen, Sari
Diallo, Mamou
Xu, Yingqi
Matthews, Steve J.
Zavialov, Anton V.
author_facet Pakharukova, Natalia
Garnett, James A.
Tuittila, Minna
Paavilainen, Sari
Diallo, Mamou
Xu, Yingqi
Matthews, Steve J.
Zavialov, Anton V.
author_sort Pakharukova, Natalia
collection PubMed
description 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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spelling pubmed-46545872015-11-25 Structural Insight into Archaic and Alternative Chaperone-Usher Pathways Reveals a Novel Mechanism of Pilus Biogenesis Pakharukova, Natalia Garnett, James A. Tuittila, Minna Paavilainen, Sari Diallo, Mamou Xu, Yingqi Matthews, Steve J. Zavialov, Anton V. PLoS Pathog Research Article 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. Public Library of Science 2015-11-20 /pmc/articles/PMC4654587/ /pubmed/26587649 http://dx.doi.org/10.1371/journal.ppat.1005269 Text en © 2015 Pakharukova et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Pakharukova, Natalia
Garnett, James A.
Tuittila, Minna
Paavilainen, Sari
Diallo, Mamou
Xu, Yingqi
Matthews, Steve J.
Zavialov, Anton V.
Structural Insight into Archaic and Alternative Chaperone-Usher Pathways Reveals a Novel Mechanism of Pilus Biogenesis
title Structural Insight into Archaic and Alternative Chaperone-Usher Pathways Reveals a Novel Mechanism of Pilus Biogenesis
title_full Structural Insight into Archaic and Alternative Chaperone-Usher Pathways Reveals a Novel Mechanism of Pilus Biogenesis
title_fullStr Structural Insight into Archaic and Alternative Chaperone-Usher Pathways Reveals a Novel Mechanism of Pilus Biogenesis
title_full_unstemmed Structural Insight into Archaic and Alternative Chaperone-Usher Pathways Reveals a Novel Mechanism of Pilus Biogenesis
title_short Structural Insight into Archaic and Alternative Chaperone-Usher Pathways Reveals a Novel Mechanism of Pilus Biogenesis
title_sort structural insight into archaic and alternative chaperone-usher pathways reveals a novel mechanism of pilus biogenesis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4654587/
https://www.ncbi.nlm.nih.gov/pubmed/26587649
http://dx.doi.org/10.1371/journal.ppat.1005269
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