Symmetry-breaking transitions in the early steps of protein self-assembly.

Symmetry-breaking transitions in the early steps of protein self-assembly.
Eur Biophys J. 2020 Mar 02;:
Authors: La Rosa C, Condorelli M, Compagnini G, Lolicato F, Milardi D, Do TN, Karttunen M, Pannuzzo M, Ramamoorthy A, Fraternali F, Collu F, Rezaei H, Strodel B, Raudino A
Abstract
Protein misfolding and subsequent self-association are complex, intertwined processes, resulting in development of a heterogeneous population of aggregates closely related to many chronic pathological conditions including Type 2 Diabetes Mellitus and Alzheimer's disease. To address this issue, here, we develop a theoretical model in the general framework of linear stability analysis. According to this model, self-assemblies of peptides with pronounced conformational flexibility may become, under particular conditions, unstable and spontaneously evolve toward an alternating array of partially ordered and disordered monomers. The predictions of the theory were verified by atomistic molecular dynamics (MD) simulations of islet amyloid polypeptide (IAPP) used as a paradigm of aggregation-prone polypeptides (proteins). Simulations of dimeric, tetrameric, and hexameric human-IAPP self-assemblies at physiological electrolyte concentration reveal an alternating distribution of the smallest domains (of the order of the peptide mean length) formed by partially ordered (mainly β-strands) and disordered (turns and coil) arrays. Periodicity disappears upon weakening...

Source: European Biophysics Journal : EBJ - March 1, 2020 Category: Physics Authors: La Rosa C, Condorelli M, Compagnini G, Lolicato F, Milardi D, Do TN, Karttunen M, Pannuzzo M, Ramamoorthy A, Fraternali F, Collu F, Rezaei H, Strodel B, Raudino A Tags: Eur Biophys J Source Type: research