How short is too short for amyloid fibrils?: Molecular dynamics of oligomers of infectious prion core structures.

ABSTRACT: In many proteinopathies, the relative conformations of amyloid fibrils versus smaller oligomers remain unclear. Most tissue-derived isolates of infectious prion protein (PrP) prions are predominantly fibrillar. A few studies have asserted that prion amyloid fibrils efficiently disassemble into dimeric to tetrameric "elemental bricks" under certain detergent or chaotropic conditions, but our companion paper provides strong evidence to the contrary. Given our difficulties in isolating detectable amounts of small oligomeric (2-4-mer) prions, we performed molecular dynamics simulations to test the abilities of small fragments (dimers to 25-mers) of cryo-EM-based infectious prion fibril core structures to retain their conformational integrity. We show that dimers of the aRML prion structure los

SUBMITTER: Artikis E 

PROVIDER: S-EPMC12301783 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature