The hydrophobic effect characterises the thermodynamic signature of amyloid fibril growth

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  • Juami Hermine Mariama van Gils, VU University, Amsterdam
  • ,
  • Erik van Dijk, VU University, Amsterdam
  • ,
  • Alessia Peduzzo, University of Düsseldorf
  • ,
  • Alexander Hofmann, University of Düsseldorf
  • ,
  • Nicola Vettore, University of Düsseldorf
  • ,
  • Marie P Schützmann, University of Düsseldorf
  • ,
  • Georg Groth, University of Düsseldorf
  • ,
  • Halima Mouhib, Université Paris-Est
  • ,
  • Daniel E Otzen
  • Alexander K Buell, University of Düsseldorf, Danmarks Tekniske Universitet
  • ,
  • Sanne Abeln, VU University, Amsterdam

Many proteins have the potential to aggregate into amyloid fibrils, protein polymers associated with a wide range of human disorders such as Alzheimer's and Parkinson's disease. The thermodynamic stability of amyloid fibrils, in contrast to that of folded proteins, is not well understood: the balance between entropic and enthalpic terms, including the chain entropy and the hydrophobic effect, are poorly characterised. Using a combination of theory, in vitro experiments, simulations of a coarse-grained protein model and meta-data analysis, we delineate the enthalpic and entropic contributions that dominate amyloid fibril elongation. Our prediction of a characteristic temperature-dependent enthalpic signature is confirmed by the performed calorimetric experiments and a meta-analysis over published data. From these results we are able to define the necessary conditions to observe cold denaturation of amyloid fibrils. Overall, we show that amyloid fibril elongation is associated with a negative heat capacity, the magnitude of which correlates closely with the hydrophobic surface area that is buried upon fibril formation, highlighting the importance of hydrophobicity for fibril stability.

OriginalsprogEngelsk
Artikelnummere1007767
TidsskriftPLOS Computational Biology
Vol/bind16
Nummer5
ISSN1553-7358
DOI
StatusUdgivet - maj 2020

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