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Distinct thermodyna...
Distinct thermodynamic signatures of oligomer generation in the aggregation of the amyloid-β peptide
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- Cohen, Samuel I.A. (author)
- University of Cambridge
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- Cukalevski, Risto (author)
- Lund University,Lunds universitet,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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- Michaels, Thomas C.T. (author)
- Harvard University,University of Cambridge
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- Šarić, A. (author)
- University College London
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- Törnquist, Mattias (author)
- Lund University,Lunds universitet,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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- Vendruscolo, Michele (author)
- University of Cambridge
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- Dobson, Christopher M. (author)
- University of Cambridge
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- Buell, Alexander K. (author)
- Heinrich Heine University Düsseldorf
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- Knowles, Tuomas P.J. (author)
- University of Cambridge
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- Linse, Sara (author)
- Lund University,Lunds universitet,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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(creator_code:org_t)
- 2018-03-26
- 2018
- English 9 s.
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In: Nature Chemistry. - : Springer Science and Business Media LLC. - 1755-4330 .- 1755-4349. ; 10:5, s. 523-531
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Abstract
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- Mapping free-energy landscapes has proved to be a powerful tool for studying reaction mechanisms. Many complex biomolecular assembly processes, however, have remained challenging to access using this approach, including the aggregation of peptides and proteins into amyloid fibrils implicated in a range of disorders. Here, we generalize the strategy used to probe free-energy landscapes in protein folding to determine the activation energies and entropies that characterize each of the molecular steps in the aggregation of the amyloid-β peptide (Aβ42), which is associated with Alzheimer's disease. Our results reveal that interactions between monomeric Aβ42 and amyloid fibrils during fibril-dependent secondary nucleation fundamentally reverse the thermodynamic signature of this process relative to primary nucleation, even though both processes generate aggregates from soluble peptides. By mapping the energetic and entropic contributions along the reaction trajectories, we show that the catalytic efficiency of Aβ42 fibril surfaces results from the enthalpic stabilization of adsorbing peptides in conformations amenable to nucleation, resulting in a dramatic lowering of the activation energy for nucleation.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
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- art (subject category)
- ref (subject category)
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Cohen, Samuel I. ...
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Cukalevski, Rist ...
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Michaels, Thomas ...
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Šarić, A.
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Törnquist, Matti ...
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Vendruscolo, Mic ...
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Dobson, Christop ...
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Buell, Alexander ...
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Knowles, Tuomas ...
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Linse, Sara
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
- Articles in the publication
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Nature Chemistry
- By the university
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Lund University