The structure of amyloid Aβ(1-41) is the object of many papers due to the neurodegenerative processes induced by this amyloid. One of the ways to investigate the possible structural forms other than the amyloid is to incorporate the fragment of this peptide into the chain of immunoglobulin. Fragment Aβ(18-41) presented within the CDR3 loop region of a shark immunoglobulin new antigen receptor single-variable domain antibody is the object of this analysis. The structure of this hybrid is available in the PDB and analyzed based on the fuzzy oil drop model. The aim is to define the status of this fragment, revealing the possible fitting to the ordered form of the hydrophobic core. Simultaneously, the verification of the predisposition to complexation is possible.
2
Dostęp do pełnego tekstu na zewnętrznej witrynie WWW
The analysis of amyloid structures is much easier recently due to the availability of the solid-state nuclear magnetic resonance technique, which allows the determination of the 3D structure of amyloid forms. The amyloidogenic polypeptide Aβ(1-40) (PDB ID 2M9R, 2M9S) in its soluble form is the object of analysis in this paper. The solubility of this polypeptide is reached due to the presence of a complexed ligand: polyphenol ε-viniferin glucoside. Two forms of complexes available in the PDB were taken for analysis with respect to the presence of a hydrophobic core in the 3D structure of these complexes. The idealized hydrophobic core structure assumed to be accordant with the 3D Gauss function distribution was taken as the pattern. The aim of this analysis is the possible further comparison to the structures of the hydrophobic core present in amyloids. It is shown that the discordant (versus the 3D Gauss function) fragments present in amyloids appear accordant in the discussed complexes.
3
Dostęp do pełnego tekstu na zewnętrznej witrynie WWW
Despite enormous progress in molecular analysis of cancer cell genomes, the mechanism of tumorigenesis remains unclear. The information present in the genome is not limited to the DNA sequence itself. Indeed, a significant portion of this information is concealed in the spatial structure of chromatin. Ongoing scientific studies that focus on the three-dimensional structure of chromatin raise hopes of arriving at a general explanation of the cancer transformation phenomenon.
4
Dostęp do pełnego tekstu na zewnętrznej witrynie WWW
The application of the fuzzy oil drop model to the analysis of protein structure is shown using two proteins. The selection of these two examples is due to their opposite character. Two proteins were selected representing very high order and very high disorder with respect to the organized uni-central hydrophobic core in proteins (one centrally localized concentration of high hydrophobicity). These two cases are to show examples of the large spectrum of variability of local organization of the hydrophobic core in proteins. The importance of the observation presented in this paper is significant with respect to large sets of proteins discussed in separate publications.
5
Dostęp do pełnego tekstu na zewnętrznej witrynie WWW
The fuzzy oil drop model was applied to characterize the hydrophobic core structure in plant carboxylesterase. The characteristics revealed the status of β-sheets in the central part of the molecule as discordant as opposed to the expected hydrophobicity distribution. Particularly, the β-strands and helices in close proximity to the enzymatic residues recognized as discordant with respect to the ideal hydrophobicity distribution of hydrophobic core are of high importance. It is assumed that this local irregularity is the form of coding the specificity of enzymes. The protein under consideration appears to be the next example proving this assumption.
6
Dostęp do pełnego tekstu na zewnętrznej witrynie WWW
Abstract: The mechanism of specific ligand binding by proteins is discussed using the PDZ domain complexing the pentapeptide. This process is critical for clustering the membrane ion channel. The traditional model based on the Beta-sheet extension by complexed pentapeptide is interpreted as a hydrophobic core extension supported by additional Beta-strand generated by complexed pentapeptide. The explanation is based on the fuzzy oil drop model applied to the crystal structure of PDZ-pentapeptide.
7
Dostęp do pełnego tekstu na zewnętrznej witrynie WWW
Heme binding by proteins and protein-protein complexation are the processes strongly related to the biological activity of proteins. The mechanism of these processes has not been still recognised. These phenomena are presented using haemoglobin as the example. Half of the mature haemoglobin (one α-chain and one β-chain) treated as a dissociation step in haemoglobin degradation reveals a specific change in heme binding after dissociation. This phenomenon is the object of analysis that interprets the structure of both complexes (tetramer and dimer) with respect to their hydrophobic core structure. The results suggest the higher stability of the complex in the form of one α-chain and one β-chain with respect to the hydrophobic core.
The problem of structural similarity of polypeptide chains of low sequence similarity representing a similar 3D structural form has been the object of analysis of researchers engaged in the protein folding problem. Three homologous proteins of similar biological function with low sequence similarity are the objects of analysis presented in this paper. The structure of a hydrophobic core is used as the criterion for structural similarity assessment of these three proteins. The applied method allows recognition of differentiati on in topologically similar structures.
9
Dostęp do pełnego tekstu na zewnętrznej witrynie WWW
Sequence-to-structure relation is one of the major objects of the analysis of protein folding problem. The pair of two small proteins (domains) of similar structure (β-hairpin/α-helix/β-hairpin) generated by the chains of similar length (about 60 amino acids) with very low sequence similarity (15%) is the object of the comparable analysis of 3D structure. The criterion for similarity estimation is the status of polypeptide chain with respect to the hydrophobic core structure. The fuzzy oil drop model is applied to reveal the differentiated status of fragments of the well-defined secondary structure. This analysis allows the interpretation of the structure in other than the geometric form as it is made based on secondary structure classification. The two compared highly similar proteins appear to be different with respect to the hydrophobic core structure.
W ramach artykułu przestawiono metodykę diagnostyki, regeneracji oraz regulacji wtryskiwaczy Common Rail na profesjonalnych stołach probierczych. Maszyna EPS 815 firmy Bosch umożliwia sprawdzenie i naprawę wszystkich rodzajów wtryskiwaczy firmy BOSCH, zgodnie z wymogami i standardami stawianymi przez producenta. W artykule przedstawiono przykładową diagnostykę wtryskiwaczy na tych stanowiskach oraz stosowane metody regeneracji i kodowania wtryskiwaczy po regeneracji.
EN
The article presents the methodology of Common Rail injector diagnostic, regeneration and regulation with use of professional test stands. The EPS 815 machine can be used to test and repair all BOSCH injectors fully satisfying the producer requirements and standards. The article describes an example injector diagnosis with use of such test stand and additionally presents appropriate injector regeneration and encoding techniques.
11
Dostęp do pełnego tekstu na zewnętrznej witrynie WWW
Congo red (CR) and other self-assembling compounds creating supramolecular structures of rod- or ribbon-like architecture form specific complexes with cellulose and also with many proteins, including antibodies bound to the antigen and amyloids in particular. The mechanism of complexation and structure of these complexes are still poorly recognized despite the importance of the problem for medicine. This work proposes the progress in electron microscopy studies of amyloid-dye complexes by labeling supramolecular ligand CR with silver ions as a marker. Silver ions are introduced to CR carried by the strongly binding silver dye Titan yellow, which in addition form comicellar structures with CR. Silver carried by self-assembled dye molecules forms in the resulting metal nanoparticles, making the specific amyloid ligand CR perceptible in EM studies.
12
Dostęp do pełnego tekstu na zewnętrznej witrynie WWW
The fuzzy oil drop model was applied to analyze the structure of macromomycin, the apoprotein of the antitumor antibiotic auromomycin, revealing the differentiation of β-structural fragments present in β-sandwich. The seven-stranded antiparallel β-barrel and two antiparallel β-sheet ribbons represent the highly ordered geometry of the structure. However, participation in hydrophobic core formation appears different. The structure of the complete domain represents the status of the irregular hydrophobic core; however, some β-structural fragments appear to represent the hydrophobicity density distribution accordant with the idealized distribution of hydrophobicity as expected using the fuzzy oil drop model. Four β-structural fragments generating one common layer appear to be unstable in respect to the general structure of the hydrophobic core. This area is expected to be more flexible than other parts of the molecule. The protein binds the ligand – chromophore, two 2-methyl-2,4-pentanediol – in a well- defined cleft. The presence of this cleft makes the general structure of the hydrophobic core irregular (as it may be interpreted using the fuzzy oil drop model). Two short loops generated by two SS bonds fit very well to the general distribution of hydrophobicity density as expected for the model. No information about the potential amyloidogenic character of this protein is given in the literature; however, the specificity of the hydrophobicity distribution profile is found to be highly similar to the one observed in transthyretin (Banach M, Konieczny L, Roterman I. The fuzzy oil drop model, based on hydrophobicity density distribution, generalizes the influence of water environment on protein structure and function. J Theor Biol 2014;359:6–17), suggesting a possible tendency to turn to the amyloid form. A detailed analysis of macromomycin will be given, and a comparable analysis with other proteins of β-sandwich or β-barrel will be presented.
W ramach artykułu przestawiono analizy statystyczne rodzajów napraw realizowanych w analizowanej firmie obejmujące okres pięciu lat. Analiza jest oparta na bazie danych (SQL), w której zapisywane są wszystkie informacje dotyczące realizowanych zleceń. W ramach analiz określono strukturę zbioru naprawianych pojazdów oraz przeprowadzono analizę najczęstszych usterek pojazdów.
EN
The article presents a statistical analysis of car repair data gathered by an examined company over five-year time interval. It is based on a SQL database which contains information about all realized orders. The analysis defines the structure of the set of repaired car makes and additionally to find the most frequent vehicle defects.
14
Dostęp do pełnego tekstu na zewnętrznej witrynie WWW
Two of the key problems plaguing humanity – aging and carcinogenesis – are inexorably linked. While their nature seems different, their mechanisms have a lot in common. Evidence suggests that aging is the result of spontaneous synthesis and accumulation of improperly folded proteins in cells, leading to a variety of pathologies. As for carcinogenesis, it is tied to genetic mutations – permanent, covalent changes in the DNA. Both processes are random in character; however, unlike mutations, the accumulation of malformed proteins is not genetically determined. Instead, control over this process hinges upon regulating the protein exchange rate – a phenomenon that seems a likely candidate for the basic aging control mechanism. Although mutations themselves may be counteracted in a controlled manner, their effects typically cannot. The mechanisms of aging and carcinogenesis, while functionally different, remain correlated: an aging cell is rendered more susceptible to mutational changes. The rapidly growing body of information regarding aging and carcinogenesis enables a systemic approach to both these phenomena – an approach that is attempted in this review.
15
Dostęp do pełnego tekstu na zewnętrznej witrynie WWW
The role of exons can be studied on many levels, one of which pertains to protein structure. It is a well-known fact that secondary structural motifs do not directly correspond to exons: helices, β-sheets and loops have all been identified as encoded by more than one exon. The relation between exon fragments and their involvement in shaping the three-dimensional (3D) structure of a protein body is subject to ongoing studies. In particular, the role of exons in stabilizing tertiary structures can be related to the structure of the hydrophobic core of the protein. Participation of specific polypeptide fragments (single exons) in hydrophobic stabilization reveals the role played by each fragment. In the course of the presented research, exons in selected proteins have been identified on the basis of GenBank files, imported from the nucleotide database at the National Center of Biotechnology Information. Amino acid sequences representing each exon were subsequently traced to parts of 3D structural forms. The participation of each exon fragment in shaping the hydrophobic core of the protein was measured using divergence entropy calculations. It was found that each protein contains at least one exon which encodes a structural fragment in accordance with the theoretical hydrophobic core model. This implies that the likely role of at least one exon in each protein is to generate a hydrophobic core which is, in turn, responsible for tertiary structural stabilization.
16
Dostęp do pełnego tekstu na zewnętrznej witrynie WWW
This article describes the role of protein fragments encoded by individual exons. Structural analysis of the hydrophobic core on the basis of the “fuzzy oil drop” model – in whole molecules as well as in fragments encoded by specific exons – indicates that, in each protein, at least one exon encodes a fragment, which is consistent with the theoretical distribution of hydrophobicity density. Quantitative assessment of the properties of such exons in selected proteins enables the model to be applied in identifying the structural (stabilizing) role of polypeptide chains encoded by individual exons. This is viewed as a preliminary step toward future exploitation of this technique in studying the alternative splicing phenomenon.
Niektóre liotropowe układy ciekłokrystaliczne tworzące taśmowe układy micelarne mają zdolność tworzenia kompleksów z białkami pod warunkiem możliwości penetracji do wnętrza bryły białkowej. Możliwość taką stwarzają białka o niestabilnej strukturze w tym głównie białka patologiczne a także część białek należących do białek ostrej fazy. Modyfikacja ładunku białka w wyniku kompleksowania może być ujawniona w rozdziale elektroforetycznym. Dwukierunkowy rozdział elektroforetyczny z dodatkiem liganda supramolekularnego w drugim prostopadłym kierunku rozdziału pozwala na ujawnienie i izolację kompleksów z ciekłokrystalicznym ligandem. Otwiera to istotne możliwości diagnostyczne. Oczekiwane jest opracowanie numerycznej techniki ilościowej oceny proporcji ujawnionych frakcji białkowych. Wiązanie ligandów ciekłokrystalicznych okazuje się też aktualne w przypadku kompleksowania ich przez złogi amyloidowe. Czerwień Kongo jest w tym przypadku markerem specyficznym.
EN
Some lyotropic liquide crystals of ribbon-like micellar structure form complexes with proteins of unstable structure due to possible penetration to their interior. Misfolded proteins and some acute phase serum proteins belong to that group. The altered charge of proteins engaged in complexation which becomes modified by the charge of bound ligand affects electrophoretic migration and allows differentiation of ubnormal proteins from among serum proteins. Two-dimensional agarose electrophoresis of serum proteins undergone complexation with supramolecular ligand after perpendicular reorganization of migration fulfils the requirement. The exposure of misfolded proteins and their quantitative analysis has a significant diagnostic meaning. Elaboration of numerical analysis is expected. Ligands in form of liquide crystals have been found to be bound to amyloids. Congo red appeared to be the specific marker for recognition of amyloid fibrils. This type of ligand seems to be the new category of ligands complexes in form of multimolecular system.
18
Dostęp do pełnego tekstu na zewnętrznej witrynie WWW
Biological processes are controlled automatically. Registration of signals and measuring their relative strength is hence a key problem. Receptors may be relatively simple or complex. The complexity is the direct response to ambiguity of signals. If there is however a common feature of diverse signals a construction of generic receptor mechanism is usually observed. Combinatorial technique is commonly used in biological systems to decrease the complexity in reception of highly ambiguous signals.
19
Dostęp do pełnego tekstu na zewnętrznej witrynie WWW
The applicability of the model for protein folding process simulation is presented using as the test two homologous proteins of different fold: helical in 3BD1 and β-structural form in 2PIJ [L. van Dorn, T. Newlove, S. Chang, W. Ingram, M. Cordes. Biochemistry 45, 10542 (2006)]. The folding process is assumed to be directed by hydrophobic core directing the hydrophobic residues toward the center of the molecule and exposing the hydrophilic residues on the surface. The “fuzzy oil drop” model is expressed by the 3-dimensional Gauss function which mimics the external force field. The value of Gauss function is interpreted as the hydrophobicity density calculated in any point of the space of the protein body. The accordance of idealized and observed hydrophobicity distributions (calculated according to Levitt function) measured using the Kullback-Leibler divergence entropy reveals good accordance in two homological proteins of different folds. The structural differences appeared to be easily explainable on the basis of “fuzzy oil drop” model.
20
Dostęp do pełnego tekstu na zewnętrznej witrynie WWW
The recurrent 24 hours oscillations of biological activities which are generally called circadian rhythms are considered to be a mechanism allowing synchronisation of biological processes. The oscillations are generated by operation of special clock-like intra-cell devices comprising commonly transcription-translation processes as basis of measuring the time. The clock mechanism is controlled by two cooperating working out-of-phase negative feedback loops. Directly the oscillations are driven by steering signals changing the adjustment of feedback loops. They are created de novo in each cycle by complexation of synthesized proteins after their concentration reaches suitably high values. The complexes inhibit the protein synthesis in the own system while inducing it simultaneously in the cooperating one initiating in this way the next oscillation wave. The inhibition of protein synthesis is correlated with the degradation of already synthesizes molecules allowing the return to starting point of oscillation. The alignment of the proper phase of peripheral tissue cells clocks is maintained by the central brain clock – master clock.
JavaScript jest wyłączony w Twojej przeglądarce internetowej. Włącz go, a następnie odśwież stronę, aby móc w pełni z niej korzystać.