Abstract
Selected amyloid structures available in the Protein Data Bank have been subjected to a comparative analysis. Classification is based on the distribution of hydrophobicity in amyloids that differ with respect to sequence, chain length, the distribution of beta folds, protofibril structure, and the arrangement of protofibrils in each superfibril. The study set includes the following amyloids: Aβ (1–42), which is listed as Aβ (15–40) and carries the D23N mutation, and Aβ (11–42) and Aβ (1–40), both of which carry the E22Δ mutation, tau amyloid, and α-synuclein. Based on the fuzzy oil drop model (FOD), we determined that, despite their conformational diversity, all presented amyloids adopt a similar structural pattern that can be described as a ribbon-like micelle. The same model, when applied to globular proteins, results in structures referred to as “globular micelles,” emerging as a result of interactions between the proteins’ constituent residues and the aqueous solvent. Due to their composition, amyloids are unable to attain entropically favorable globular forms and instead attempt to limit contact between hydrophobic residues and water by producing elongated structures. Such structures typically contain quasi hydrophobic cores that stretch along the fibril’s long axis. Similar properties are commonly found in ribbon-like micelles, with alternating bands of high and low hydrophobicity emerging as the fibrils increase in length. Thus, while globular proteins are generally consistent with a 3D Gaussian distribution of hydrophobicity, the distribution instead conforms to a 2D Gaussian distribution in amyloid fibrils.
Highlights
The phenomenon of protein misfolding appears to be closely related to amyloid transformation, which is implicated in a number of neurodegenerative diseases [1]
According to the fuzzy oil drop model, each protein molecule was characterized by several key parameters; two variants of relative distance (RD): relative distance between observed (O)
When RD < 0.5, we could assume that a prominent hydrophobic core was present within the protein molecule
Summary
The phenomenon of protein misfolding appears to be closely related to amyloid transformation, which is implicated in a number of neurodegenerative diseases [1]. Such conditions result from pathologically aggregated protein plaques referred to as amyloids [2]. A study of 50 different disorders and their symptoms revealed the propensity of certain proteins to produce amyloid plaques in standard environmental conditions [3]. The transformation of soluble proteins into fibrils can be explained as a gradual process where cross-beta forms emerge in a relatively disorganized environment and subsequently increase in size and breadth [9]. Disordered proteins are Molecules 2019, 24, 4395; doi:10.3390/molecules24234395 www.mdpi.com/journal/molecules
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