New mechanism of amyloid fibril formation.

New mechanism of amyloid fibril formation.
Curr Protein Pept Sci. 2019 Jan 25;:
Authors: Galzitskaya O
Abstract
Polymorphism is a specific feature of the amyloid structures. We have studied the amyloid structures and the process of their formation using the synthetic and recombinant preparations of Aβ peptides and their three fragments. The fibrils of different morphology were obtained for these peptides. We suppose that fibril formation by Aβ peptides and their fragments proceeds according to the simplified scheme: destabilized monomer → ring-like oligomer → mature fibril that consists of ring-like oligomers. We are the first who did 2D reconstruction of amyloid fibrils provided that just a ring-like oligomer is the main building block in fibril of any morphology, like a cell in an organism. Taking this into account it is easy to explain the polymorphism of fibrils as well as the splitting of mature fibrils under different external actions, the branching and inhomogeneity of fibril diameters. Identification of regions in the protein chains that form the backbone of amyloid fibril is a direction in the investigation of amyloid formation. It has been demonstrated for Aβ(1-42) peptide and its fragments that their complete structure is inaccessible for the action of proteases, which is evidence of different ways of association of ring-like oligomers upon formation of fibrils. Based on the electron microscopy and mass spectrometry...

Source: Current Protein and Peptide Science - January 25, 2019 Category: Biochemistry Authors: Galzitskaya O Tags: Curr Protein Pept Sci Source Type: research