Search Results (9)

Structures composed of alternating α and β amino acids can give rise to peculiar secondary structural motifs, which could self-assemble into complex structures of controlled geometries. This work describes the self-assembly properties of an α,β-peptide, containing three units of syn H2-(2-F-Phe)-h-PheGly-OH, able to self-organize on surfaces into a fascinating supramolecular rope. This material was characterized by AFM, electronic conduction and fluorescence measurements. Molecular dynamics simulations showed that this hexapeptide can self-assemble into an antiparallel β-sheet layer, stabilized by intermolecular H-bonds, which, in turn, can self-assemble into many side-by-side layers, due to π-π interactions. As a matter of fact, we demonstrated that in this system, the presence of aromatic residues at the intramolecular interface promoted by the alternation of α,β-amino-acids in the primary sequence, endorses the formation of a super-secondary structure where the aromatic groups are close to each other, conferring to the system good electron conduction properties. This work demonstrates the capability and future potential of designing and fabricating distinctive nanostructures and efficient bioelectronic interfaces based on an α,β-peptide, by controlling structure and interaction processes beyond those obtained with α- or β-peptides alone. Full article

A super-secondary structure (SSS) is a spatially unique ensemble of secondary structural elements that determine the three-dimensional shape of a protein and its function, rendering SSSs attractive as folding cores. Understanding known types of SSSs is important for developing a deeper understanding of the mechanisms of protein folding. Here, we propose a universal PSSNet machine-learning method for SSS recognition and segmentation. For various types of SSS segmentation, this method uses key characteristics of SSS geometry, including the lengths of secondary structural elements and the distances between them, torsion angles, spatial positions of Cα atoms, and primary sequences. Using four types of SSSs (βαβ-unit, α-hairpin, β-hairpin, αα-corner), we showed that extensive SSS sets could be reliably selected from the Protein Data Bank and AlphaFold 2.0 database of protein structures. Full article

This study explored the mechanisms by which the stability of super-secondary structures of the 3β-corner type autonomously outside the protein globule are maintained in an aqueous environment. A molecular dynamic (MD) study determined the behavioral diversity of a large set of non-homologous 3β-corner structures of various origins. We focused on geometric parameters such as change in gyration radius, solvent-accessible area, major conformer lifetime and torsion angles, and the number of hydrogen bonds. Ultimately, a set of 3β-corners from 330 structures was characterized by a root mean square deviation (RMSD) of less than 5 Å, a change in the gyration radius of no more than 5%, and the preservation of amino acid residues positioned within the allowed regions on the Ramachandran map. The studied structures retained their topologies throughout the MD experiments. Thus, the 3β-corner structure was found to be rather stable per se in a water environment, i.e., without the rest of a protein molecule, and can act as the nucleus or “ready-made” building block in protein folding. The 3β-corner can also be considered as an independent object for study in field of structural biology. Full article

Biological activity regulation by protein post-translational modification (PTM) is critical for cell function, development, differentiation, and survival. Dysregulation of PTM proteins is present in various pathological conditions, including rheumatoid arthritis (RA). RA is a systemic autoimmune disease that primarily affects joints, and there are three main types of protein PTMs associated with the development of this disease, namely, glycosylation, citrullination, and carbamylation. Glycosylation is important for the processing and presentation of antigen fragments on the cell surface and can modulate immunoglobulin activity. The citrullination of autoantigens is closely associated with RA, as evidenced by the presence of antibodies specific to citrullinated proteins in the serum of patients. Carbamylation and dysregulation have recently been associated with RA development in humans.In this study, we performed an overview analysis of proteins with post-translational modifications associated with the development of RA adverted in peer-reviewed scientific papers for the past 20 years. As a result of the search, a list of target proteins and corresponding amino acid sequences with PTM in RA was formed. Structural characteristics of the listed modified proteins were extracted from the Protein Data Bank. Then, molecular dynamics experiments of intact protein structures and corresponding structures with PTMs were performed regarding structures in the list announced in the ProtDB service. This study aimed to conduct a molecular dynamics study of intact proteins and proteins, including post-translational modification and protein citrullination, likely associated with RA development. We observed another exhibition of the fundamental physics concept, symmetry, at the submolecular level, unveiled as the autonomous repetitions of outside the protein structural motif performance globule corresponding to those in the whole protein molecule. Full article

Proteins expressed during the cell cycle determine cell function, topology, and responses to environmental influences. The development and improvement of experimental methods in the field of structural biology provide valuable information about the structure and functions of individual proteins. This work is devoted to the study of supersecondary structures of proteins and determination of their structural motifs, description of experimental methods for their detection, databases, and repositories for storage, as well as methods of molecular dynamics research. The interest in the study of supersecondary structures in proteins is due to their autonomous stability outside the protein globule, which makes it possible to study folding processes, conformational changes in protein isoforms, and aberrant proteins with high productivity. Full article

β-barrel membrane proteins have several important biological functions, including transporting water and solutes across the membrane. They are active in the highly hydrophobic environment of the lipid membrane, as opposed to soluble proteins, which function in a more polar, aqueous environment. Globular soluble proteins typically have a hydrophobic core and a polar surface that interacts favorably with water. In the fuzzy oil drop (FOD) model, this distribution is represented by the 3D Gauss function (3DG). In contrast, membrane proteins expose hydrophobic residues on the surface, and, in the case of ion channels, the polar residues face inwards towards a central pore. The distribution of hydrophobic residues in membrane proteins can be characterized by means of 1–3DG, a complementary 3D Gauss function. Such an analysis was carried out on the transmembrane proteins of bacteria, which, despite the considerable similarities of their super-secondary structure (β-barrel), have highly differentiated properties in terms of stabilization based on hydrophobic interactions. The biological activity and substrate specificity of these proteins are determined by the distribution of the polar and nonpolar amino acids. The present analysis allowed us to compare the ways in which the different proteins interact with antibiotics and helped us understand their relative importance in the development of the resistance mechanism. We showed that beta barrel membrane proteins with a hydrophobic core interact less strongly with the molecules they transport. Full article

New advances in protein post-translational modifications (PTMs) have revealed a complex layer of regulatory mechanisms through which PTMs control cell signaling and metabolic pathways, contributing to the diverse metabolic phenotypes found in cancer. Using conformational templates and the three-dimensional (3D) environment investigation of proteins in patients with colorectal cancer, it was demonstrated that most PTMs (phosphorylation, acetylation, and ubiquitination) are localized in the supersecondary structures (helical pairs). We showed that such helical pairs are represented on the outer surface of protein molecules and characterized by a largely accessible area for the surrounding solvent. Most promising and meaningful modifications were observed on the surface of vitamin D-binding protein (VDBP), complement C4-A (CO4A), X-ray repair cross-complementing protein 6 (XRCC6), Plasma protease C1 inhibitor (IC1), and albumin (ALBU), which are related to colorectal cancer developing. Based on the presented data, we propose the impact of the observed modifications in immune response, inflammatory reaction, regulation of cell migration, and promotion of tumor growth. Here, we suggest a computational approach in which high-throughput analysis for identification and characterization of PTM signature, associated with cancer metabolic reprograming, can be improved to prognostic value and bring a new strategy to the targeted therapy. Full article

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. Full article

We present an alternative approach to protein 3D folding prediction based on determination of rules that specify distribution of “favorable” residues, that are mainly responsible for a given fold formation, and “unfavorable” residues, that are incompatible with that fold, in polypeptide sequences. The process of determining favorable and unfavorable residues is iterative. The starting assumptions are based on the general principles of protein structure formation as well as structural features peculiar to a protein fold under investigation. The initial assumptions are tested one-by-one for a set of all known proteins with a given structure. The assumption is accepted as a “rule of amino acid distribution” for the protein fold if it holds true for all, or near all, structures. If the assumption is not accepted as a rule, it can be modified to better fit the data and then tested again in the next step of the iterative search algorithm, or rejected. We determined the set of amino acid distribution rules for a large group of beta sandwich-like proteins characterized by a specific arrangement of strands in two beta sheets. It was shown that this set of rules is highly sensitive (~90%) and very specific (~99%) for identifying sequences of proteins with specified beta sandwich fold structure. The advantage of the proposed approach is that it does not require that query proteins have a high degree of homology to proteins with known structure. So long as the query protein satisfies residue distribution rules, it can be confidently assigned to its respective protein fold. Another advantage of our approach is that it allows for a better understanding of which residues play an essential role in protein fold formation. It may, therefore, facilitate rational protein engineering design. Full article