Linking Protein Folding to Amyloid Formation

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 dogma, globular proteins can misfold to form amyloid fibrils. Here, we present a general concept for the link between folding and misfolding. 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.