Different Synergy in Amyloids and Biologically Active Forms of Proteins.

Piotr Fabian,Leszek Konieczny,Irena Roterman,Katarzyna Stapor,Magdalena Ptak-Kaczor,Mateusz Banach

doi:10.3390/ijms20184436

Abstract

Protein structure is the result of the high synergy of all amino acids present in the protein. This synergy is the result of an overall strategy for adapting a specific protein structure. It is a compromise between two trends: The optimization of non-binding interactions and the directing of the folding process by an external force field, whose source is the water environment. The geometric parameters of the structural form of the polypeptide chain in the form of a local radius of curvature that is dependent on the orientation of adjacent peptide bond planes (result of the respective Phi and Psi rotation) allow for a comparative analysis of protein structures. Certain levels of their geometry are the criteria for comparison. In particular, they can be used to assess the differences between the structural form of biologically active proteins and their amyloid forms. On the other hand, the application of the fuzzy oil drop model allows the assessment of the role of amino acids in the construction of tertiary structure through their participation in the construction of a hydrophobic core. The combination of these two models—the geometric structure of the backbone and the determining of the participation in the construction of the tertiary structure that is applied for the comparative analysis of biologically active and amyloid forms—is presented.

Highlights

The issue of amyloid transformations is a central point of interest for specialists in the field of protein structure analysis [1,2,3,4,5,6,7,8,9,10]
The availability of the amyloid form of the tau protein has revealed the possibility of polymorphism of fibril structures [17] or the α-synuclein structure, where only a selected fragment of the chain forms the fibril form [18]
The structure of the amyloid form ASyn available in the PDB database shows the presence of fibrillar order only in the segment 30–100

Summary

Introduction

The issue of amyloid transformations is a central point of interest for specialists in the field of protein structure analysis [1,2,3,4,5,6,7,8,9,10]. The availability of the amyloid form of the tau protein has revealed the possibility of polymorphism of fibril structures [17] or the α-synuclein structure (called as ASyn in this paper), where only a selected fragment of the chain forms the fibril form [18]. Immunoglobulin V domain is available in biologically active amyloid structural forms. These structures are available in addition to numerous forms of the Fab fragment in the form of a dimer called Bence-Jones (two lambda light chains) [20] and in the form of amyloid [21]. The availability of the two last mentioned proteins creates the possibility of comparative analysis, which may suggest a potential mechanism of amyloid transformation

Methods

Results

Conclusion