On the Dependence of Prion and Amyloid Structure on the Folding Environment.

Leszek Konieczny,Irena Roterman,Piotr Nowakowski,Tomasz Gubała,Krzysztof Gądek,Katarzyna Stapor,Piotr Fabian

doi:10.3390/ijms222413494

Leszek Konieczny, Irena Roterman + Show 5 more

Open Access

https://doi.org/10.3390/ijms222413494

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Abstract

Currently available analyses of amyloid proteins reveal the necessity of the existence of radical structural changes in amyloid transformation processes. The analysis carried out in this paper based on the model called fuzzy oil drop (FOD) and its modified form (FOD-M) allows quantifying the role of the environment, particularly including the aquatic environment. The starting point and basis for the present presentation is the statement about the presence of two fundamentally different methods of organizing polypeptides into ordered conformations—globular proteins and amyloids. The present study shows the source of the differences between these two paths resulting from the specificity of the external force field coming from the environment, including the aquatic and hydrophobic one. The water environment expressed in the fuzzy oil drop model using the 3D Gauss function directs the folding process towards the construction of a micelle-like system with a hydrophobic core in the central part and the exposure of polarity on the surface. The hydrophobicity distribution of membrane proteins has the opposite characteristic: Exposure of hydrophobicity at the surface of the membrane protein with an often polar center (as in the case of ion channels) is expected. The structure of most proteins is influenced by a more or less modified force field generated by water through the appropriate presence of a non-polar (membrane-like) environment. The determination of the proportion of a factor different from polar water enables the assessment of the protein status by indicating factors favoring the structure it represents.

Highlights

The protein folding problem has been the subject of analysis for many years [1,2]
The fuzzy oil drop (FOD) model uses a 3D Gauss function to express the effect inducing the formation of a centric hydrophobic core
The FOD-M model introduces modifications resulting from the need to take into account the hydrophobic environment for proteins anchored in the membrane

Summary

Introduction

The protein folding problem has been the subject of analysis for many years [1,2]. Amyloids are formed without the need for mutation and represent a significantly different structural form resulting in the formation of linear fibrils that do not have much in common with the phenomenon of protein complexation [4,5]. Side chains are mainly involved in protein complexation, while in the structure of amyloids a fundamental role is played by interactions resulting from the abundant presence of beta-structural secondary structures. This structural form is based on a network of interchain hydrogen bonds formed by backbone atoms [6]

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