caa a22 4500 528786202 20190713030956.0 cr unu---uuuuu 180924s2016 xx s 000 0 eng 10.3929/ethz-b-000116640 doi 10.1038/ncomms10948 doi (ETHRESEARCH)oai:www.research-collection.ethz.ch:20.500.11850/116640 Kinetic analysis reveals the diversity of microscopic mechanisms through which molecular chaperones suppress amyloid formation [Elektronische Daten] [Paolo Arosio, Thomas C.T. Michaels, Sara Linse, Cecilia Månsson, Cecilia Emanuelsson, Jenny Presto, Jan Johansson, Michele Vendruscolo, Christopher M. Dobson, Tuomas P.J. Knowles] Nat Commun Open access ethresearch 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. Creative Commons Attribution 4.0 International http://creativecommons.org/licenses/by/4.0 ethresearch Arosio Paolo joint author Michaels Thomas C.T. joint author Linse Sara joint author Månsson Cecilia joint author Emanuelsson Cecilia joint author Presto Jenny joint author Johansson Jan joint author Vendruscolo Michele joint author Dobson Christopher M. joint author Knowles Tuomas P.J. joint author Nature Communications London : Nature Publishing Group 7, p. 10948 2041-1723 http://hdl.handle.net/20.500.11850/116640 text/html WWW-Backlink auf das Repository (Open access) 1 Journal Article ethresearch ETHRESEARCH 856 40 http://hdl.handle.net/20.500.11850/116640 text/html WWW-Backlink auf das Repository (Open access) ETHRESEARCH 700 1- Arosio Paolo joint author ETHRESEARCH 700 1- Michaels Thomas C.T. joint author ETHRESEARCH 700 1- Linse Sara joint author ETHRESEARCH 700 1- Månsson Cecilia joint author ETHRESEARCH 700 1- Emanuelsson Cecilia joint author ETHRESEARCH 700 1- Presto Jenny joint author ETHRESEARCH 700 1- Johansson Jan joint author ETHRESEARCH 700 1- Vendruscolo Michele joint author ETHRESEARCH 700 1- Dobson Christopher M. joint author ETHRESEARCH 700 1- Knowles Tuomas P.J. joint author ETHRESEARCH 773 0- Nature Communications London : Nature Publishing Group 7, p. 10948 2041-1723 BK010053 XK010053 XK010000 ETHRESEARCH ETHRESEARCH ETHRESEARCH Journal Article Open access