Formation of nucleoproteids provides implementation of the major functions nucleic acids (see) — reproduction, transfer and implementation of genetic information. Depending on type nucleinic to - you, being a part of a complex, distinguish dezoksiribonuk-leoproteida (DNP) and ribonucleoproteins (RNP). The proteins forming Complexes with nucleinic to-tami can be divided into two groups.
One contact electrostatic bonds preferential two-spiral polynucleotides and by that stabilize their secondary structure, others, affinity to-rykh to one-spiral polynucleotides above, than to two-spiral, at linkng with two-spiral polynucleotide chains destabilize their secondary structure. Proteins of a gene of the 5th phage of fd, a gene 32 phages of T4, enzyme ribonuclease, the protein of SI secreted from ribosomes and destabilizing secondary structure of RNA, etc. Nek-rye from the proteins destabilizing dvukhnitevy nucleinic to - you, have a polydomain structure concern the last. Each domain is responsible for interaction with a certain ligand. On process of a kompleksiro-vaniye of a polynucleotide chain with proteins considerable impact is exerted by also topological organization of molecules nucleinic to - t (e.g., linear, ring or the DNA superspiral form). A number of structural, regulatory proteins, including and enzymes, have different affinity to the specific sequences in the molecules DNA which are in superspiral or relaksirovanny forms.
In some cases the defining moment at interaction nucleinic to - the t with proteins is existence of the specific nucleotide sequences in a polynucleotide chain. At the same time sizes of association constants of protein with the specific sequences of nucleotides in a molecule nucleinic to - you are many times higher, than sizes of association constants of the same protein with any other nucleotide sequences. It belongs, e.g., to the nucleoproteid representing the site of molecule DNA which is characterized by the specific nucleotide sequences (operator) with is white - a lump - repressorom, blocking initiation of a transcription corresponding template-RNA. Assume that specificity of process of formation of this complex is caused by emergence of hydrogen bindings between the remains of certain amino acids in a molecule of protein-repressora and functional groups of nitrogen bases of the operator. Besides, the complex is stabilized by electrostatic interactions between the DNA phosphatic groups and basic groups of protein-repressora, and within the last and squirrels - proteinaceous contacts. Interaction of protein-repressora with the denatured DNA, and also the operator changed as a result of mutations less effectively. Basic value has that in primary structure of many operators the symmetric sequences of nucleotides are found. It theoretically allows reorganization of the operator from a double helix in structure like «hairpin», edges probably and is learned by protein. This assumption in a nek-swarm of degree is confirmed by big sizes of association constants of protein-repressora from the ring DNA which is in a superspiral form.
Interaction between components H. has also idiosyncrasies depending on structurally functional purpose of a nukleoproteidny complex in natural biostructures. E.g., in viruses force and the nature of communication of the interacting groups H. significantly depend on the sizes, chemical structure, type of symmetry proteinaceous capsids, structures of proteinaceous subunits and a look nucleinic to - you (DNA or RNA) a virus. So, spherical viruses in direct contact with molecules of protein have only peripheral sites nucleinic to - you, the minimum contact between these connections is a consequence of what. In palochkoobrazny or threadlike viruses nucleinic to - that on all the extent is shipped in protein that leads to more expressed interaction between them. Interaction between components H. is the important factor defining biol, properties of virions, their inactivation, sensitivity to mutagens etc.
For education pro-template-RNA (about-MRNK) and its transport from the place of synthesis to a nuclear membrane the difficult polisomopodobny RNP-complexes which are formed of a molecule about-MRNK and the proteinaceous structures which are consistently located on it — an informofer have essential value. In formation of these complexes a noticeable role is played by electrostatic forces. The similar type of interactions takes place and in informosomes — the structures localized in cytosol and representing difficult complexes between template-RNA and several polypeptides.
One more representative of N. yav-tsya ribosomes — intracellular structures, in to-rykh protein synthesis is carried out. Sites of ribosomal RNA, different in primary structure and the organization, define an arrangement of proteinaceous subunits in subparticles of ribosomes. At the same time the act of a kompleksirovaniye leads to structural reorganization of certain nucleotide sequences of RNA. The majority of ribosomal proteins has osnovny character that is caused by the high content in them of arginine and a lysine that emphasizes the significant contribution of electrostatic interactions to formation of the RNA-protein complex. It is confirmed by dissociation of rather discrete groups of proteins under the influence of high salt contents of monovalent metals before almost full deproteinization of ribosomal RNA. However this type of interactions does not exhaust all bonds between RNA and proteins in ribosomes. So, e.g., nitridation of the remains of tyrosine, and also modification of the remains of a lysine or methionine in the corresponding proteins of ribosomes almost completely breaks to the RNA-belko-Vyya interactions. Philosophy of nucleinic and proteinaceous «recognition» in ribosomes and in other RNP-complexes are found still insufficiently out.
In transfer and implementation of genetic information in cells of eukaryotes the main role is played nucleinic to - you. The DNA complexes are fullestly studied with histones (see) and protamins (see). Molecules of protamins consist approximately of 45 amino-acid remains, nearly 3/4 of them are the remains of arginine. However in the majority of cells of eukaryotes the main proteinaceous component H. are histones. Their molecules contain apprx. 25% of the main amino acids (preferential arginine and a lysine). On electrophoretic mobility histones divide into 5 main fractions — H1, N2a, N2v, NZ, N4, and proteins of these fractions differ from each other and based on the ratio of the remains of a lysine and arginine in molecules. Within one fraction of a molecule of histones can differ by quantity and the place of a rapolozheniye of the modified amino acids (acetylized, metilirovanny, fosfo-rilirovanny, ribozilirovanny). Nek-ry fractions of histones have subfractions. In cells with a repressed genome the H1 fraction is sometimes replaced on a histone of H5, the protein A24 representing histone N2a covalently connected with polypeptide ubikhitiny is a part of nucleohistone. As in a mitosis protein A24 is absent, the assumption is made that protein A24 is one of the factors interfering mitotic condensation of DNP in interphase. Molecules of histones and (or) their complexes with each other connect to DNA preferential at the expense of electrostatic bonds between the is WILD negatively charged phosphates and positively charged groups of the remains of the main amino acids of histones. The structure of a complex arising at the same time is periodic, the repeating element — the nucleosoma contains depending on a source of allocation of N. of DNA from 160 to 240 nucleotide couples long and on two molecules of each of histones N2a, N2v, NZ, N4. In a nucleosoma allocate the main part («core») containing regardless of a source of allocation of N. constant amount of DNA (140 — 145 couples of nucleotides) and 8 molecules of the histones (so-called octameasures — on two molecules of each histone: N2a, N2v, NZ, N4) associated with each other by means of hydrophobic interactions of the unpolar blocks. As model of a core of a nucleosoma the disk with a diameter of 11 nanometers and 5,7 nanometers thick can serve, and DNA in a B-form in the form of a spiral with a diameter of 9 nanometers and a step of 2,8 nanometers is cast over a proteinaceous kernel. The main parts of nucleosoma are connected among themselves by the segments of DNA which are not entering the main particles. Length of this connecting site of DNA — «linker» is equal to a difference between lengths of DNA of all nucleosoma and its main part. Thus the variation of lengths of linker causes heterogeneity of nucleosoma by amount of DNA which is contained in them. Perhaps, length of a linker is defined by the nature related a histone of H1 (one molecule on one nucleosoma) and negistonovy proteins.
Negistonovy proteins chromatin (see) very geterogenna on the structure; by means of an electrophoresis depending on type of cells it is identified from several tens to hundreds of separate fractions of such proteins. Their pier. the weight (weight) make from 5000 to 200 000. Isoelectric points are in range from 3 to 10. Negistonovy proteins H. contain a large number asparaginic and glutaminic to - t. They exchange much quicker, than histones, and unlike them are synthesized during all mitotic cycle. Negistonovy connected with nucleosoma it is white ki represent rather low-molecular proteins containing a large number diamino-and dicarbonic amino acids, differing in high electrophoretic mobility therefore in literature they are designated as NANOMETERS of a G-squirrel (English high mobility group). At nek-ry proteins of this group (the NANOMETER G 1 and NANOMETER G 2) noted distinction in affinity to the sverkhsiiralny and relaksirovanny DNA forms. During the processing of DNP directly in kernels of cells the enzymes hydrolyzing preferential those sites of DNA to-rye represent active genes in this cell, from DNP nek-ry negistonovy proteins are released. It allows to consider that negistonovy proteins (preferential NANOMETER G 14 and NANOMETER G 17) are connected with nucleosoma of functionally active chromatin.
Nucleosoma represent dynamic educations: at the corresponding parameters of the environment when electrostatic pushing away exceeds forces of hydrophobic interaction, nucleosoma are developed. At mechanical stretching length of DNP fibrilla increases, and the picture, characteristic of nucleosoma, at the X-ray crystallographic analysis disappears. Introduction to the circle of the agents who are donors of intermolecular bonds (e.g., polycations), leads to fixing of structure of open nucleosoma. Emergence in the environment of the connections competing for intermolecular communication (preferential, polyanions), causes condensation of DNP again. Structural changes of nucleosoma indicate existence of polymorphism (topomor-fizm) of DNP already at the level of packaging of these educations. The possibility of the choice from a number of alternative structures of DNP is, apparently, one of fundamentals of epigenesis because the phenotype can be considered as a possibility of the choice from several ways of implementation of information transmitted through DNA of chromosomes. The fact that formation of nucleosoma is followed by superspiralling of the closed DNA is basic. It is necessary to consider that the superspiral is always negative, i.e. it is opposite to a sign of a double helix. With increase in density of rounds of a superspiral enough DNA extended areas having, apparently, functional value begin to reveal what the fact that the frequency of initiation of a transcription with increase in density of a superspiral increases demonstrates to. It is essential that the sverkhspi-ralization stimulates also a recombination. Assume that in the mechanism of genetic recombinations the possibility of their regulation through change of the DNP structural organization is put. Transfer of DNA from the superspiral form induced by formation of nucleosoma in relaksirovanny can be carried out by one of enzymes of group of topoisomerases, activity to-rogo is regulated by its interaction with a histone of H1.
Data on the organization of nucleosoma are obtained on the drugs DNP emitted from natural biostructures, however believe, as in cells of DNP are organized in a similar way. In the presence as a part of DNP of a histone H1 of a nucleosoma densely adjoin to each other, forming fibrilla diameter apprx. 10 nanometers. The fact that the coefficient of linear packaging of DNA is equal in a nucleosoma about 7, and coefficient of linear packaging of DNA of a metaphase chromosome makes size about 104, indicates existence of levels of the DNP organization of higher, than level of the organization of nucleosoma. The DNP fibrilla with a diameter of 20 — 30 nanometers which is found in interfazny kernels of cells can be received by superspiral packaging of fibrilla with a diameter of 10 nanometers in structure of type of the solenoid or packaging of nucleosoma in particles, each of to-rykh consists of 6 — 10 nucleosoma, the nukleo-measures which received the name, or superbida. At the same time the coefficient of linear packaging of DNA is equal to about 40. Mechanisms of the DNP organization in structures of higher order are insufficiently clear. This organization is specific to each type of the cells differing on the nature of synthesis of RNA. The processes of condensation or dekondensation of DNP happening at this level have essential value for functioning of a genome, «including» or «switching off» big blocks of genes, napr, at a differentiation of cells, an inactivation of the condensed sites of chromatin in interfazny kernels, an inactivation of segments of polytene chromosomes etc.
Thus, the structural dynamics of nucleosoma defining a possibility of their polymorphism is, apparently, one of mechanisms of regulation of functional activity of a genome and its changes through recombinations. Changes of activity of a genome happen also at disturbance in N. of a ratio of histone/DNA. E.g., the decrease in quantity or speed of synthesis of histones caused by shortage of the genes controlling synthesis of histones at a drosophila reduces the size of a ratio of histone/DNA in N., increases matrix activity of X-chromosome and maintains activity of the gene transferred to heterochromatin. Increase of size of the relation of histone/DNA leads to repression of certain genes. Changes of an expression (expression) of genes happen also at the modification of histones which is carried out in the course of a cellular cycle. So, acetylation of histones correlates with activation of a transcription genes, and their phosphorylation — with replication and formation of mitotic chromosomes. Generally all types of modification of histones are implemented in DNP through change of their electrostatic interactions with DNA.
Changes of relationship of DNA and proteins in N. take place at a malignancy, nek-ry chromosomal diseases, etc. E.g., at a Down syndrome in a number of sites of kernels of cells of DNP are more condensed, than normal. At the same time local sites of DNA H. get to other microenvironment that leads to change of constants of their linkng with the corresponding substrate, i.e. change of an expression of a number of genes if the last are involved in these sites.
As a result of action of mutagens physical. and the chemical nature in DNP there are numerous damages: partial dissociation of N., formation of «stitchings» between DNA and nek-ry proteins H., disintegration of some number of N. on nucleosoma, disturbance of structurization of nucleoproteid. At the same time proteins, intercepting free radicals, partially protect DNA in N., reducing destruction of nitrogen bases and number of single and pair gaps. Have Nek-rye from the listed damages genetic, and a part — functional effects.
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