Influence of the Aqueous Environment on Protein Structure—A Plausible Hypothesis Concerning the Mechanism of Amyloidogenesis

Irena Roterman,Leszek Konieczny,Barbara Kalinowska,Mateusz Banach

doi:10.3390/e18100351

Abstract

The aqueous environment is a pervasive factor which, in many ways, determines the protein folding process and consequently the activity of proteins. Proteins are unable to perform their function unless immersed in water (membrane proteins excluded from this statement). Tertiary conformational stabilization is dependent on the presence of internal force fields (nonbonding interactions between atoms), as well as an external force field generated by water. The hitherto the unknown structuralization of water as the aqueous environment may be elucidated by analyzing its effects on protein structure and function. Our study is based on the fuzzy oil drop model—a mechanism which describes the formation of a hydrophobic core and attempts to explain the emergence of amyloid-like fibrils. A set of proteins which vary with respect to their fuzzy oil drop status (including titin, transthyretin and a prion protein) have been selected for in-depth analysis to suggest the plausible mechanism of amyloidogenesis.

Highlights

The search for algorithms which enable simulation of protein folding and tertiary structure prediction has been ongoing for more than 50 years [1]
The titin domain is an example of a structure which contains a prominent hydrophobic core (RD = 0.382)
This low value indicates that the observed distribution (Table 2) closely corresponds to theoretical values and that the protein contains a concentration of hydrophobicity density at its center, encapsulated in a hydrophilic shield

Summary

Introduction

The search for algorithms which enable simulation of protein folding and tertiary structure prediction has been ongoing for more than 50 years [1]. Nature itself provides an interesting study subject in the form of misfolded proteins (nothing in common with mutation) which are the origin of the so-called misfolding diseases, where incorrectly folded proteins (or proteins which undergo undesirable conformational changes) create insoluble fibrillary aggregations, leading to a variety of degenerative conditions [5]. This phenomenon drives the search for algorithms which would explain how proteins attain their native 3D form as well as indicate why the folding process sometimes produces incorrect results [6,7]

Methods

Results

Conclusion