Biochemistry (Moscow) (v.76, #13)

Interspecies transmission of prions by E. G. Afanasieva; V. V. Kushnirov; M. D. Ter-Avanesyan (1375-1384).
Mammalian prions are infectious agents of proteinaceous nature that cause several incurable neurodegenerative diseases. Interspecies transmission of prions is usually impeded or impossible. Barriers in prion transmission are caused by small interspecies differences in the primary structure of prion proteins. The barriers can also depend on the strain (variant) of a transmitted prion. Interspecies barriers were also shown for yeast prions, which define some heritable phenotypes. Yeast prions reproduce all the main traits of prion transmission barriers observed for mammals. This allowed to show that the barrier in prion transmission can be observed even upon copolymerization of two prionogenic proteins. Available data allow elucidation of the mechanisms that impede prion transmission or make it impossible.
Keywords: interspecies barrier; prions; PrP; [PSI +]; yeast; Saccharomyces cerevisiae

Different types of structures closed into cycles are widespread at all the levels of structural organization of proteins. β-Hairpins, triple-stranded β-sheets, and βαβ-units represent simple structural motifs closed into cycles by systems of hydrogen bonds. Secondary closing of these simple motifs into larger cycles by means of different superhelices, split β-hairpins, or SS-bridges results in formation of complex structural motifs such as abcd-units, φ-motifs, five- and seven-segment α/β-motifs, etc. At the level of tertiary structure many proteins and domains fold into structures closed into cylinders. Apparently, closing the motifs and domains into cycles and cylinders results in formation of more cooperative and stable structures as compared with open ones, and this may be the reason for high frequencies of occurrence of the motifs in proteins.
Keywords: βαβ-unit; β-sheet; handedness; split β-hairpin; structural motif; superhelix

Horseradish peroxidase: Modulation of properties by chemical modification of protein and heme by G. S. Zakharova; I. V. Uporov; V. I. Tishkov (1391-1401).
Horseradish peroxidase (HRP) is one of the most studied enzymes of the plant peroxidase superfamily. HRP is also widely used in different bioanalytical applications and diagnostic kits. The methods of genetic engineering and protein design are now widely used to study the catalytic mechanism and to improve properties of the enzyme. Here we review the results of another approach to HRP modification—through the chemical modification of amino acids or prosthetic group of the enzyme. Computer models of HRPs with modified hemes are in good agreement with the experimental data.
Keywords: horseradish peroxidase; HRP; heme; chemical modification; catalytic properties; stability; computer modeling

Y-box-binding protein 1 (YB-1) and its functions by I. A. Eliseeva; E. R. Kim; S. G. Guryanov; L. P. Ovchinnikov; D. N. Lyabin (1402-1433).
This review describes the structure and functions of Y-box binding protein 1 (YB-1) and its homologs. Interactions of YB-1 with DNA, mRNAs, and proteins are considered. Data on the participation of YB-1 in DNA reparation and transcription, mRNA splicing and translation are systematized. Results on interactions of YB-1 with cytoskeleton components and its possible role in mRNA localization are discussed. Data on intracellular distribution of YB-1, its redistribution between the nucleus and the cytoplasm, and its secretion and extracellular functions are summarized. The effect of YB-1 on cell differentiation, its involvement in extra- and intracellular signaling pathways, and its role in early embryogenesis are described. The mechanisms of regulation of YB-1 expression in the cell are presented. Special attention is paid to the involvement of YB-1 in oncogenic cell transformation, multiple drug resistance, and dissemination of tumors. Both the oncogenic and antioncogenic activities of YB-1 are reviewed. The potential use of YB-1 in diagnostics and therapy as an early cancer marker and a molecular target is discussed.
Keywords: YB-1; Y-box binding proteins; regulation of gene expression; DNA repair; transcription; translation; oncogenesis; oncomarker; multidrug resistance; metastasis

RNA-binding proteins play a significant role in many processes of RNA metabolism, such as splicing and processing, regulation of DNA transcription and RNA translation, etc. Among the great number of RNA-binding proteins, so-called RNA-chaperones occupy an individual niche; they were named for their ability to assist RNA molecules to gain their accurate native spatial structure. When binding with RNAs, they possess the capability of altering (melting) their secondary structure, thus providing a possibility for formation of necessary intramolecular contacts between individual RNA sites for proper folding. These proteins also have an additional helper function in RNA-RNA and RNA-protein interactions. Members of such class of the RNA-binding protein family are Sm and Sm-like proteins (Sm-Like, LSm). The presence of these proteins in bacteria, archaea, and eukaryotes emphasizes their biological significance. These proteins are now attractive for researchers because of their implication in many processes associated with RNAs in bacterial and archaeal cells. This review is focused on a comparison of architecture of bacterial and archaeal LSm proteins and their interaction with different RNA molecules.
Keywords: Hfq; Sm-like protein; quaternary structure; RNA-protein interaction

5S rRNA and ribosome by G. M. Gongadze (1450-1464).
5S rRNA is an integral component of the ribosome of all living organisms. It is known that the ribosome without 5S rRNA is functionally inactive. However, the question about the specific role of this RNA in functioning of the translation apparatus is still open. This review presents a brief history of the discovery of 5S rRNA and studies of its origin and localization in the ribosome. The previously expressed hypotheses about the role of this RNA in the functioning of the ribosome are discussed considering the unique location of 5S rRNA in the ribosome and its intermolecular contacts. Based on analysis of the current data on ribosome structure and its functional complexes, the role of 5S rRNA as an intermediary between ribosome functional domains is discussed.
Keywords: 5S rRNA; ribosomal proteins; intermolecular interactions; ribosome; translation

Structure-function investigations of bacterial photosynthetic reaction centers by M. M. Leonova; T. Yu. Fufina; L. G. Vasilieva; V. A. Shuvalov (1465-1483).
During photosynthesis light energy is converted into energy of chemical bonds through a series of electron and proton transfer reactions. Over the first ultrafast steps of photosynthesis that take place in the reaction center (RC) the quantum efficiency of the light energy transduction is nearly 100%. Compared to the plant and cyanobacterial photosystems, bacterial RCs are well studied and have relatively simple structure. Therefore they represent a useful model system both for manipulating of the electron transfer parameters to study detailed mechanisms of its separate steps as well as to investigate the common principles of the photosynthetic RC structure, function, and evolution. This review is focused on the research papers devoted to chemical and genetic modifications of the RCs of purple bacteria in order to study principles and mechanisms of their functioning. Investigations of the last two decades show that the maximal rates of the electron transfer reactions in the RC depend on a number of parameters. Chemical structure of the cofactors, distances between them, their relative orientation, and interactions to each other are of great importance for this process. By means of genetic and spectral methods, it was demonstrated that RC protein is also an essential factor affecting the efficiency of the photochemical charge separation. Finally, some of conservative water molecules found in RC not only contribute to stability of the protein structure, but are directly involved in the functioning of the complex.
Keywords: bacterial photosynthesis; photosynthetic reaction center; site-directed mutagenesis; photosynthetic electron transfer; purple bacteria

Molecular mechanism of actin-myosin motor in muscle by N. A. Koubassova; A. K. Tsaturyan (1484-1506).
The interaction of actin and myosin powers striated and smooth muscles and some other types of cell motility. Due to its highly ordered structure, skeletal muscle is a very convenient object for studying the general mechanism of the actin-myosin molecular motor. The history of investigation of the actin-myosin motor is briefly described. Modern concepts and data obtained with different techniques including protein crystallography, electron microscopy, biochemistry, and protein engineering are reviewed. Particular attention is given to X-ray diffraction studies of intact muscles and single muscle fibers with permeabilized membrane as they give insight into structural changes that underlie force generation and work production by the motor. Time-resolved low-angle X-ray diffraction on contracting muscle fibers using modern synchrotron radiation sources is used to follow movement of myosin heads with unique time and spatial resolution under near physiological conditions.
Keywords: actin; myosin; muscle; ATPase; structure; X-ray diffraction

Tropomyosin: Double helix from the protein world by I. A. Nevzorov; D. I. Levitsky (1507-1527).
This review concerns the structure and functions of tropomyosin (TM), an actin-binding protein that plays a key role in the regulation of muscle contraction. The TM molecule is a dimer of α-helices, which form a coiled-coil. Recent views on the TM structure are analyzed, and special attention is concentrated on those structural traits of the TM molecule that distinguish it from the other coiled-coil proteins. Modern data are presented on TM functional properties, such as its interaction with actin and ability to move on the surface of actin filaments, which underlies the regulation of the actin-myosin interaction upon contraction of skeletal and cardiac muscles. Also, part of the review is devoted to analysis of the effects of mutations in TM genes associated with muscle diseases (myopathies) on the structure and functions of TM.
Keywords: tropomyosin; coiled-coil proteins; regulation of muscle contraction

Chemotaxis: Movement, direction, control by A. V. Vorotnikov (1528-1555).
This review focuses on basic principles of motility in different cell types, formation of the specific cell structures that enable directed migration, and how external signals are transduced into cells and coupled to the motile machinery. Feedback mechanisms and their potential role in maintenance of internal chemotactic gradients and persistence of directed migration are highlighted.
Keywords: cell motility; directed migration; chemotaxis; signal transduction; feedback regulation

Many human diseases are caused by malfunction of basic types of cellular activity such as proliferation, differentiation, apoptosis, cell polarization, and migration. In turn, these processes are associated with different routes of intracellular signal transduction. A number of model systems have been designed to study normal and abnormal cellular and molecular processes associated with pathogenesis. The developing eye of the fruit fly Drosophila melanogaster is one of these systems. The sequential development of compound eyes of this insect makes it possible to model human neurodegenerative diseases and mechanisms of carcinogenesis. In this paper we overview the program of the eye development in Drosophila, with emphasis on intracellular signaling pathways that regulate this complex process. We discuss in detail the roles of the Notch, Hedgehog, TGFβ, Wnt, and receptor tyrosine kinase signaling pathways in Drosophila eye development and human pathology. We also briefly describe the modern methods of experimentation with this model organism to analyze the function of human pathogenic proteins.
Keywords: Drosophila; eye development; signal transduction; cancer; Notch; Hedgehog; Wnt; RTK; model