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Breakdown of supersaturation barrier links protein folding to amyloid formation

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  • Masahiro Noji, Osaka Univ, Osaka University
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  • Tatsushi Samejima, Osaka Univ, Osaka University
  • ,
  • Keiichi Yamaguchi, Osaka Univ, Osaka University
  • ,
  • Masatomo So, Osaka Univ, Osaka University
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  • Keisuke Yuzu, Kobe Univ, Kobe University, Grad Sch Human Dev & Environm
  • ,
  • Eri Chatani, Kobe Univ, Kobe University, Grad Sch Human Dev & Environm
  • ,
  • Yoko Akazawa-Ogawa, National Institute of Advanced Industrial Science and Technology (AIST)
  • ,
  • Yoshihisa Hagihara, National Institute of Advanced Industrial Science and Technology (AIST)
  • ,
  • Yasushi Kawata, Tottori University
  • ,
  • Kensuke Ikenaka, Osaka Univ, Osaka University
  • ,
  • Hideki Mochizuki, Osaka Univ, Osaka University
  • ,
  • József Kardos, Eotvos Lorand University
  • ,
  • Daniel E Otzen
  • Vittorio Bellotti, University College London, University of Pavia
  • ,
  • Johannes Buchner, Technical University of Munich
  • ,
  • Yuji Goto, Osaka Univ, Osaka University

The thermodynamic hypothesis of protein folding, known as the "Anfinsen's dogma" states that the native structure of a protein represents a free energy minimum determined by the amino acid sequence. However, inconsistent with the Anfinsen's dogma, globular proteins can misfold to form amyloid fibrils, which are ordered aggregates associated with diseases such as Alzheimer's and Parkinson's diseases. Here, we present a general concept for the link between folding and misfolding. We tested the accessibility of the amyloid state for various proteins upon heating and agitation. Many of them showed Anfinsen-like reversible unfolding upon heating, but formed amyloid fibrils upon agitation at high temperatures. We show that folding and amyloid formation are separated by the supersaturation barrier of a protein. Its breakdown is required to shift the protein to the amyloid pathway. Thus, the breakdown of supersaturation links the Anfinsen's intramolecular folding universe and the intermolecular misfolding universe.

OriginalsprogEngelsk
Artikelnummer120
TidsskriftCommunications Biology
Vol/bind4
Nummer1
Antal sider10
DOI
StatusUdgivet - jan. 2021

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