- “INTERACTION SITES OF EUKARYOTIC DNA WITH THE STEROID HORMONE-APOLIPOPROTEIN AI COMPLEXES”
Velichko E.Ju., Gimautdinova O.I.
Institute of Biochemistry, Siberian Branch of the Russian Academy of Medical Sciences, Timakova str. 2, Novosibirsk 630117, RussiaPreviously it was shown that glucocorticoids and high-density lipoproteins (HDL) exert a cooperative effect enhancing the RNA and protein biosynthesis in white rat liver [1]. The mechanism of this effect differs from the known mechanism of glucocorticoid induction of gluconeogenesis enzymes. Further studies showed that the active form of hormone operating in a nucleus together with apolipoprotein A-I (apoA-I) is its reduced form, tetrahydrocortisol (THC), which was previously considered to be an inert metabolite. Enzymatic analysis of DNA associated with the tetrahydrocortisol-apoAI complex allowed estimation of the number of newly arisen nuclease-sensitive regions (2 per 100 kbp), their distribution in the rat genome and possible structure [2].
In the present work we studied interaction protein – steroid hormone complexes with various synthetic oligonucleotides and the sensitive of nucleotide sequences to nuclease S1 and DNAase was determined. We suggest a functional role of THC-apoAI complex being similar to the function of the transcription factor/cofactor changing the DNA structure in binding sites. Direct localization of numerous single-stranded regions forming in DNA under the action of THC-apoAI complex seems to be a difficult task. Therefore, we experimentally tested several synthetic oligonucleotides for the specificity of their interaction with steroid hormone – apoAI complexes.
References.
1. Panin L.E., Svechnikova I.G., and Mayanskaya N.N., 1995. Cooperative effect of the high density lipoproteins and adaptive hormons in a chromatin activation of rat liver. Ukrainskii biokhim. J. (Russia), 67, 64-70.
2. Panin L.E., Gimautdinova O.I., Kuznetsov P.A, Akimzhanova M.V., Tuzikov F.V. 2002. The effect of tetrahydrocortisol-apolipoprotein A-I complex on the secondary structure of eukariotic DNA and its interaction with RNA-polymerase. Biochemistry. (Russia), 67, 953-958. - “Modeling co-evolution of protozoa using Evolution Constructor (discrete approach)”
Lashin S.
Institute of Cytology and Genetics SB RAS, 630090, Novosibirsk, Lavrentyev aven., 10, Russia - “Evolutionary algorithms for mathematical models of gene network identification”
Lashin S.
Institute of Cytology and Genetics SB RAS, 630090, Novosibirsk, Lavrentyev aven., 10, Russia - “Aromorphoses and the adaptive molecular evolution: hedgehog and wingless aignaling cascades genes.”
Gunbin K.V., Omelyanchuk L.V., Kolchanov N.A.
Institute of Cytology and Genetics SB RAS, 630090, Novosibirsk, Lavrentyev aven., 10, RussiaAdaptive evolution of the signal cascades components determining multicellular organisms development – is the basis of understanding reasons and mechanisms of the ontogenesis evolution. In this work, the character of the evolution of several genes participating in Hedgehog (Hh) and Wingless (Wg) signaling cascade was analyzed. This signaling cascades is the universal molecular mechanism, implicated in control of multicellular organisms morphogenesis. It was shown that: 1) the adaptive evolution of the central cascade components (the transcription factors, the morphogene and the morphogene receptors) correlates with large aromorphoses (for example, appearance of large taxons of the Bilateria); 2) as a rule, after the formation of gene paralogs at least one paralog evolves adaptively; 3) the adaptive evolution of the signal cascade enzymes, which are unspecific for developmental processes, is not correlated with aromorphoses. - “Semantically rich ontology of anatomical structure and development for Arabidopsis thaliana (L.)”
Ponomaryov D.,
Institute of Informatics Systems, Russian Academy of Sciences, Novosibirsk, RussiaThis talk describes principles of capturing plant anatomy and development in a formal way for building applied ontologies. The principles are illustrated by example of Arabidopsis thaliana ontology, built as a wrapper for navigation in AGNS2 database, which contains gene expression data and phenotype data of Arabidopsis. General constructs in the ontology, as well as its features and other potential applications will be examined.Abstract:
Ontology of a subject domain is a set of statements that are true for every possible situation in the subject domain. The aim of our work is a formal ontological description of anatomical structure and development of Arabidopsis thaliana (wild type), which serves as the target subject domain.
Several information sources (TAIR, Gramene etc.), called simultaneously controlled vocabularyy and ontology, have been proposed recently for anatomy and development of plants. Containing basic is-a and part-of relations, they cannot be called ontologies in the strict sense of term, as they state that each anatomy element (and the whole plant) at every moment consists of the same fixed number of its sub-elements. Unfortunately, this does not correspond to the real nature of the subject domain we are aimed at. Instead, one should capture the fact that anatomy element structure changes within development process. This means that we should be able to express not only development of one structures into others, but also changes in the number of contained entities, as well as containers for anatomy elements.
The proposed ontology consists of a core structure for expressing statements like “anatomy element X at stage Sx exists in anatomy element Y at stage Sy” (where Sx and Sy are development stages of X and Y respectively) and is filled in with facts from Arabidopsis development studies. In general, the problem of describing anatomy structures in development (without taking spatial orientation into account) was reduced to ordering and inheritance of development stages. - “Introduction of bioinformatical approach in the study of protein ubiquitylation”
Gainullin M.
Central Research Laboratory, State Medical Academy, Nizhniy Novgorod, RussiaUbiquitin is a small (76 amino acids) protein that has an ability to be linked to other intracellular proteins via a covalent isopeptide bond. Such post-translational modification of target proteins named “ubiquitylation” possesses a signal function and leads to the development of biological effects of ubiquitin. Enzyme systems ligating ubiquitin to proteins or catalyzing branched multiubiquitin chain formation were extensively investigated. Several isopeptidases which release free ubiquitin and unaffected protein were also discovered. Like other post-translational modifications, ubiqutylation is a mechanism by which protein function is regulated in eukaryotes. Ubiquitin is involved in protein degradation via an intracellular ATP-dependent proteolytic system and may mediate a multitude of non-proteolytic events.
Experimental approaches of studying several ubiquitin effects proved difficult, because of the complexity of a ubiquitin system, composed of distinct ubiquitin-dependent pathways. Despite of rapidly growing number of experimental evidences on protein ubiquitylation, especially accumulation of proteomic data, many of the ubiquitin-dependent regulatory mechanisms remain enigmatic.
Diversity of known biological effects of ubiquitylation is realized through modification of a wide variety of target proteins. We take advantages of the bioinformatical approach to reveal direct effects of ubiquitylation on a single protein level as well as on enzymes, constituting a metabolic pathway. From this analysis we can deduce different modes of ubiquitin action affecting active site accessibility, conformational flexibility of polypeptide chain and protein oligomerization. Thus, a new universal mechanism of ubiquitin action, concerning its direct influence on protein functional activity, is suggested. And as far as ubiquitylation is a reversible modification, such mechanism of enzymatic activity regulation can play a significant role in cell metabolism.
To fill the general need for collecting, systematizing and analysis of experimental data concerning ubiquitylation we have developed a new resource, UbiProt Database, a knowledgebase of ubiquitylated proteins. The database contains retrievable information about overall characteristics of a particular protein, ubiquitylation properties and features, respective ubiquitylation/ deubiquitylation machinery and literature references reflecting experimental evidence of ubiquitylation of a mentioned protein. UbiProt is available at http://ubiprot.org.ru/.
Bioinformatical approach is considered to be useful for better understanding of ubiquitin system, could help predict its new functions and clarify questions that remain unsolved, such as specificity of target protein selection. - “Computer modeling of potential ways of HCV proteins- molecular evolution and prediction of targets for antiviral drugs.”
Krestyanova M.,
Novosibirsk State UniversityAt least 3 percent of the world’s population is infected with HCV, which offers serious health threat because it cause the chronic hepatitis C, which leads (to), cirrhosis and hepatocellular carcinoma. The danger of virus is that no vaccine is currently available to prevent the hepatitis C, primarily because the virus has many subtypes that change rapidly. The mutation rate of HCV is approximately 1,92 * 10-3 base substitutions per site per year, which results in considerable genetic heterogeneity throughout the genome and allows the virus to escape from immune response. Thus it is obvious that hepatitis C drug development is a vital issue.
We worked out the method searching potential interactions between HCV and human proteins, which allows to predict the evolution of HCV. The essence of method is to search regions having structural similarity with the functional sites but differ from real sites in aminoacid composition. These regions can become functional sites after certain mutations. In this work we used the PDBSiteScan program, which handles and searches active sites, binding sites and posttranslational modification sites in 3D protein structure by pairwise structural comparison of a protein with each representative of these sites from the PDBSite database collection.
New method was applied for searching potential functional sites in viral proteins NS3 and NS5B. In NS3 3 unknown functional sites were found: annexin-binding, cdk2-binding and TRKA-receptor-binding sites. In RNA polymerase NS5B NTF2-binding, NFAT-binding and CDK2-binding sites were found. The obtained sites may serve objects of furtherAWARD WINNERSOral presentations:
1st Prize
Gainullin M.
Central Research Laboratory, State Medical Academy, Nizhniy Novgorod, Russia
“Introduction of bioinformatical approach in the study of protein ubiquitylation”2nd Prize
Gunbin K.V.
Institute of Cytology and Genetics SB RAS, 630090, Novosibirsk, Lavrentyev aven., 10, Russia
“Aromorphoses and the adaptive molecular evolution: hedgehog and wingless aignaling cascades genes.”3rd Prize
Ponomaryov D.
Institute of Informatics Systems, Russian Academy of Sciences, Novosibirsk, Russia
“Semantically rich ontology of anatomical structure and development for Arabidopsis thaliana (L.)”Poster Presentation:
Lashin S.,
Institute of Cytology and Genetics SB RAS, 630090, Novosibirsk, Lavrentyev aven., 10, Russia
(1) Modeling co-evolution of protozoa using Evolution Constructor (discrete approach)
(2) Evolutionary algorithms for mathematical models of gene network identification.
