AVZ is supported by the Finnish Academy (grants 140959 and 273075; http://sciencenordic.com/partner/academy-finland) and Sigrid Juselius Foundation (grant 2014; www.sigridjuselius.fi/foundation). SMis supported by the Wellcome Trust (Senior Investigator Award 100280, Programme grant 079819; http://www.wellcome.ac.uk) The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

A Busch

AA Berry

Anton V. Zavialov

AP Tomaras

AV Zavialov

D Choudhury

D Verger

DL Hung

FG Sauer

G Phan

H Remaut

J Marchant

JA Garnett

James A. Garnett

JG Bann

Joseph D Mougous

JS Pinkner

M Nishiyama

M Pellecchia

MA Rendon

Mamou Diallo

Minna Tuittila

N Pakharukova

Natalia Pakharukova

R Bao

R Pouttu

Sari Paavilainen

SP Nuccio

Steve J. Matthews

V Zav'yalov

X Yu

XD Yu

YF Li

Yingqi Xu

PLoS Pathogens

PubMed

Pakharukova, N

Garnett, JA

Tuittila, M

Paavilainen, S

Diallo, M

Xu, Y

Matthews, SJ

Zavialov, AV

Queen Mary Research Online

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

<p>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.</p

Pakharukova, Natalia

Garnett, J.A.

Tuittila, Minna

Paavilainen, Sari

Diallo, Mamou

Xu, Yingqi

Matthews, S.J.

Zavialov, A.V.

Name not available

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

James A Garnett

Steve J Matthews

Anton V Zavialov

Directory of Open Access Journals

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

<div><p>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 <i>Acinetobacter baumannii</i> Csu and <i>Escherichia coli</i> 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.</p></div

Natalia Pakharukova (631544)

James A. Garnett (631545)

Minna Tuittila (631549)

Sari Paavilainen (828771)

Mamou Diallo (828772)

Yingqi Xu (412556)

Steve J. Matthews (828773)

Anton V. Zavialov (631551)

FigShare

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.</p

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

Abstract

Similar works

Full text

Available Versions

Queen Mary Research Online

Name not available

Directory of Open Access Journals

FigShare

King's Research Portal

Public Library of Science (PLOS)

Spiral - Imperial College Digital Repository

Wageningen Yield