Abstract

The role of the environment in amyloid formation based on the fuzzy oil drop model (FOD) is discussed here. This model assumes that the hydrophobicity distribution within a globular protein is consistent with a 3D Gaussian (3DG) distribution. Such a distribution is interpreted as the idealized effect of the presence of a polar solvent—water. A chain with a sequence of amino acids (which are bipolar molecules) determined by evolution recreates a micelle-like structure with varying accuracy. The membrane, which is a specific environment with opposite characteristics to the polar aquatic environment, directs the hydrophobic residues towards the surface. The modification of the FOD model to the FOD-M form takes into account the specificity of the cell membrane. It consists in “inverting” the 3DG distribution (complementing the Gaussian distribution), which expresses the exposure of hydrophobic residues on the surface. It turns out that the influence of the environment for any protein (soluble or membrane-anchored) is the result of a consensus factor expressing the participation of the polar environment and the “inverted” environment. The ratio between the proportion of the aqueous and the “reversed” environment turns out to be a characteristic property of a given protein, including amyloid protein in particular. The structure of amyloid proteins has been characterized in the context of prion, intrinsically disordered, and other non-complexing proteins to cover a wider spectrum of molecules with the given characteristics based on the FOD-M model.

Highlights

  • The issue of neurodegenerative diseases is obviously related to amyloids [1,2]

  • The introduced distribution described by the “complement” function in the form (1-3D Gaussian (3DG)) represents the hydrophobic membrane environment, where exposure of the hydrophobic residues is expected

  • The amyloid transformation associated with a significant increase in the value of the K parameter (Table 1) indicates the need for an external factor modifying the nature of the environment that favors the structural transformation leading to the formation of the amyloid form

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Summary

Introduction

The issue of neurodegenerative diseases is obviously related to amyloids [1,2]. In this discussion, one should distinguish the phenomenon of amyloidosis occurring in the human body [3,4,5,6,7,8] compared to in vitro experiments [9,10,11,12,13,14,15,16]. The main point of many works is the recognition of the mechanism of amyloid transformation [17,18,19,20]. One of the proposed approaches links amyloid transformation with intrinsically disordered proteins [21,22,23,24,25,26]

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