Filamentous Aggregates of Tau Proteins Fulfil Standard Amyloid Criteria Provided by the Fuzzy Oil Drop (FOD) Model.

Leszek Konieczny,Dawid Dułak,Małgorzata Gadzała,Irena Roterman,Mateusz Banach,Zdzisław Wiśniowski,Magdalena Ptak

doi:10.3390/ijms19102910

Leszek Konieczny, Dawid Dułak + Show 5 more

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https://doi.org/10.3390/ijms19102910

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Abstract

Abnormal filamentous aggregates that are formed by tangled tau protein turn out to be classic amyloid fibrils, meeting all the criteria defined under the fuzzy oil drop model in the context of amyloid characterization. The model recognizes amyloids as linear structures where local hydrophobicity minima and maxima propagate in an alternating manner along the fibril’s long axis. This distribution of hydrophobicity differs greatly from the classic monocentric hydrophobic core observed in globular proteins. Rather than becoming a globule, the amyloid instead forms a ribbonlike (or cylindrical) structure.

Highlights

The origin of amyloid transformation has attracted scientific attention for more than 35 years—at least since being acknowledged as the cause of various neurodegenerative disorders [1]
fuzzy oil drop (FOD)—Fuzzy Oil Drop model RD—Relative Distance—The divergence entropy introduced by Kullback and Leibler used to express the distance between two compared profiles is of entropy category it requires an introduction of reference distribution
The same chain conforms to the model when analyzed as part of the complex. This means that chain B creates suitable conditions for chain A to produce a shared hydrophobic core that is consistent with the 3D Gaussian

Summary

Introduction

The origin of amyloid transformation has attracted scientific attention for more than 35 years—at least since being acknowledged as the cause of various neurodegenerative disorders [1]. The proteins of high content of intrinsically disordered structural forms seem to be the candidates ready for partially folded state which may transform to disordered aggregates with low packing [5,6]. Emergence of fibrillary structures is thought of as the result of involvement of intrinsically disordered proteins, especially at early phases of the folding process [7]. Reaching the form of highly packed structuralised aggregates that are based mainly on β-structural forms opens the possibility for the unlimited elongation of highly packed ordered amyloid form [8]. The presence of Beta-structural form (cross Beta) allows for the propagation due to the possible H-bonds system to be organised on both sites

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