Breakdown of Supersaturation Barrier Links Protein Folding to Amyloid Formation

Overview

Journal Commun Biol

Specialty Biology

Date 2021 Jan 27

PMID 33500517

Citations 20

Authors

Masahiro Noji

Tatsushi Samejima

Keiichi Yamaguchi

Masatomo So

Keisuke Yuzu

Eri Chatani

Yoko Akazawa-Ogawa

Yoshihisa Hagihara

Yasushi Kawata

Kensuke Ikenaka

Hideki Mochizuki

Jozsef Kardos

Daniel E Otzen

Vittorio Bellotti

Johannes Buchner

Yuji Goto

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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