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The hydrophobic effect characterises the thermodynamic signature of amyloid fibril growth

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