Identification and nanomechanical characterization of the fundamental single-strand protofilaments of amyloid α-synuclein fibrils.

ABSTRACT: The formation and spreading of amyloid aggregates from the presynaptic protein α-synuclein in the brain play central roles in the pathogenesis of Parkinson's disease. Here, we use high-resolution atomic force microscopy to investigate the early oligomerization events of α-synuclein with single monomer angstrom resolution. We identify, visualize, and characterize directly the smallest elementary unit in the hierarchical assembly of amyloid fibrils, termed here single-strand protofilaments. We show that protofilaments form from the direct molecular assembly of unfolded monomeric α-synuclein polypeptide chains. To unravel protofilaments' internal structure and elastic properties, we manipulated nanomechanically these species by atomic force spectroscopy. The single-molecule scale identificati

SUBMITTER: Ruggeri FS 

PROVIDER: S-EPMC6048494 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature