Breakdown of supersaturation barrier links protein folding to amyloid formation

Masahiro Noji, Tatsushi Samejima, Keiichi Yamaguchi, Masatomo So, Keisuke Yuzu, Eri Chatani, Yoko Akazawa-Ogawa, Yoshihisa Hagihara, Yasushi Kawata, Kensuke Ikenaka, Hideki Mochizuki, József Kardos, Daniel E Otzen, Vittorio Bellotti, Johannes Buchner, Yuji Goto*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review


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.

Original languageEnglish
Article number120
JournalCommunications Biology
Number of pages10
Publication statusPublished - Jan 2021


Dive into the research topics of 'Breakdown of supersaturation barrier links protein folding to amyloid formation'. Together they form a unique fingerprint.

Cite this