Structural insights into a yeast prion illuminate nucleation and strain diversity

摘要: Self-perpetuating changes in the conformations of amyloidogenic proteins play vital roles normal biology and disease. Despite intense research, architecture conformational conversion amyloids remain poorly understood. Amyloid conformers Sup35 are molecular embodiment yeast prion known as [PSI], which produces heritable phenotype through self-perpetuating protein folding. Here we determine nature Sup35's cooperatively folded amyloid core, use this information to investigate central questions biology. Specific segments core form intermolecular contacts a 'Head-to-Head', 'Tail-to-Tail' fashion, but 'Central Core' is sequestered intramolecular contacts. The Head acquires productive interactions first, these nucleate assembly. Variations length interfaces structural basis distinct 'strains', produce variant phenotypes vivo. These findings resolve several problems have broad implications for other amyloids.