Structure of the Hydrophobic Core Determines the 3D Protein Structure-Verification by Single Mutation Proteins.

Mateusz Banach,Leszek Konieczny,Piotr Fabian,Katarzyna Stapor,And Irena Roterman

doi:10.3390/biom10050767

Mateusz Banach, Leszek Konieczny + Show 3 more

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https://doi.org/10.3390/biom10050767

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Abstract

Four de novo proteins differing in single mutation positions, with a chain length of 56 amino acids, represent diverse 3D structures: monomeric 3α and 4β + α folds. The reason for this diversity is seen in the different structure of the hydrophobic core as a result of synergy leading to the generation of a system in which the polypeptide chain as a whole participates. On the basis of the fuzzy oil drop model, where the structure of the hydrophobic core is expressed by means of the hydrophobic distribution function in the form of a 3D Gaussian distribution, it has been shown that the composition of the hydrophobic core in these two structural forms is different. In addition, the use of a model to determine the structure of the early intermediate in the folding process allows to indicate differences in the polypeptide chain geometry, which, combined with the construction of a common hydrophobic nucleus as an effect of specific synergy, may indicate the reason for the diversity of the folding process of the polypeptide chain. The results indicate the need to take into account the presence of an external force field originating from the water environment and that its active impact on the formation of a hydrophobic core whose participation in the stabilization of the tertiary structure is fundamental.

Highlights

The three-dimensional structure of the protein is perceived and defined by means of a description of the geometric structure of the polypeptide chain expressed as secondary and super-secondary structures
The aim of the present work is to show the possibility of the presence of different forms of the hydrophobic core as an effect of specific synergy, which, depending on the sequence (1 mutation in the chain of 56 amino acids) leads to different forms of protein
The whole protein molecule shows the compliance status of the O and T distribution. This means that the proportion of hydrophilic to hydrophobic residues guarantees the construction of a surface that is large enough for the size of the hydrophobic core

Summary

Introduction

The three-dimensional structure of the protein is perceived and defined by means of a description of the geometric structure of the polypeptide chain expressed as secondary and super-secondary structures. Proteins are characterized by various forms: helical, β-structural, sandwich, propeller, and others as super-secondary forms and various quaternary forms. Discussing the structural diversity of proteins is one of the basic topics of biochemistry textbooks [1]. In the initial period of operation of the Protein Data Bank (PDB) [2], each subsequent structure appearing in the collections of this database was treated as a source of information on the structure of proteins. After several years of PDB operation, it turned out that the structures consist of similar systems built of helices and β-beta sheets differing only in their mutual orientation. There were forms referred to as ‘new folds’—structures revealing surprising conformations mainly at the level of super-secondary structure [3,4]. Visual analysis of a large number of proteins, still evaluates their diversity as surprisingly high

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