Characterizing the amyloid core region of the tumor suppressor protein p16 using a limited proteolysis and peptide-based approach.

The human tumor suppressor p16 is a small monomeric protein that can form amyloid structures. Formation of p16 amyloid fibrils is induced by oxidation which creates an intermolecular disulfide bond. The conversion into amyloid is associated with a change from an all α-helical structure into β-sheet fibrils.

Amyloid formation and depolymerization of tumor suppressor p16 are regulated by a thiol-dependent redox mechanism.

The conversion of a soluble protein into polymeric amyloid structures is a process that is poorly understood. Here, we describe a fully redox-regulated amyloid system in which cysteine oxidation of the tumor suppressor protein p16 leads to rapid amyloid formation. We identify a partially-structured disulfide-bonded dimeric intermediate species that subsequently assembles into fibrils.