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Kinetic analysis reveals the diversity of microscopic mechanisms through which molecular chaperones suppress amyloid formation

Arosio, Paolo; Michaels, Thomas C T; Linse, Sara LU ; Månsson, Cecilia LU ; Emanuelsson, Cecilia LU ; Presto, Jenny; Johansson, Jan; Vendruscolo, Michele; Dobson, Christopher M. and Knowles, Tuomas P J (2016) In Nature Communications 7.
Abstract

It is increasingly recognized that molecular chaperones play a key role in modulating the formation of amyloid fibrils, a process associated with a wide range of human disorders. Understanding the detailed mechanisms by which they perform this function, however, has been challenging because of the great complexity of the protein aggregation process itself. In this work, we build on a previous kinetic approach and develop a model that considers pairwise interactions between molecular chaperones and different protein species to identify the protein components targeted by the chaperones and the corresponding microscopic reaction steps that are inhibited. We show that these interactions conserve the topology of the unperturbed reaction... (More)

It is increasingly recognized that molecular chaperones play a key role in modulating the formation of amyloid fibrils, a process associated with a wide range of human disorders. Understanding the detailed mechanisms by which they perform this function, however, has been challenging because of the great complexity of the protein aggregation process itself. In this work, we build on a previous kinetic approach and develop a model that considers pairwise interactions between molecular chaperones and different protein species to identify the protein components targeted by the chaperones and the corresponding microscopic reaction steps that are inhibited. We show that these interactions conserve the topology of the unperturbed reaction network but modify the connectivity weights between the different microscopic steps. Moreover, by analysing several protein-molecular chaperone systems, we reveal the striking diversity in the microscopic mechanisms by which molecular chaperones act to suppress amyloid formation.

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Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
7
publisher
Nature Publishing Group
external identifiers
  • Scopus:84961620982
ISSN
2041-1723
DOI
10.1038/ncomms10948
language
English
LU publication?
yes
id
234bd89d-2583-4579-9b1f-440692bb82ff
date added to LUP
2016-06-29 12:17:28
date last changed
2016-11-27 04:41:25
@misc{234bd89d-2583-4579-9b1f-440692bb82ff,
  abstract     = {<p>It is increasingly recognized that molecular chaperones play a key role in modulating the formation of amyloid fibrils, a process associated with a wide range of human disorders. Understanding the detailed mechanisms by which they perform this function, however, has been challenging because of the great complexity of the protein aggregation process itself. In this work, we build on a previous kinetic approach and develop a model that considers pairwise interactions between molecular chaperones and different protein species to identify the protein components targeted by the chaperones and the corresponding microscopic reaction steps that are inhibited. We show that these interactions conserve the topology of the unperturbed reaction network but modify the connectivity weights between the different microscopic steps. Moreover, by analysing several protein-molecular chaperone systems, we reveal the striking diversity in the microscopic mechanisms by which molecular chaperones act to suppress amyloid formation.</p>},
  author       = {Arosio, Paolo and Michaels, Thomas C T and Linse, Sara and Månsson, Cecilia and Emanuelsson, Cecilia and Presto, Jenny and Johansson, Jan and Vendruscolo, Michele and Dobson, Christopher M. and Knowles, Tuomas P J},
  issn         = {2041-1723},
  language     = {eng},
  month        = {03},
  publisher    = {ARRAY(0x7c09d88)},
  series       = {Nature Communications},
  title        = {Kinetic analysis reveals the diversity of microscopic mechanisms through which molecular chaperones suppress amyloid formation},
  url          = {http://dx.doi.org/10.1038/ncomms10948},
  volume       = {7},
  year         = {2016},
}