Characterizing the amyloid core region of the tumor suppressor protein p16^INK4a using a limited proteolysis and peptide-based approach.

ABSTRACT: The human tumor suppressor p16^INK4a is a small monomeric protein that can form amyloid structures. Formation of p16^INK4a 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. Currently, structural insights into p16^INK4a amyloid fibrils are lacking. Here, we investigate the amyloid-forming regions of this tumor suppressor using isotope-labeling limited-digestion mass spectrometry analysis. We discover two key regions that likely form the structured core of the amyloid. Further investigations using thioflavin-T fluorescence assays, electron microscopy, and solution nuclear magnetic resonance spectroscopy of shorter pe

SUBMITTER: Heath SG 

PROVIDER: S-EPMC11375262 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature