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Biology of regulatory proteins. Regulatory function of proteins

Biology of regulatory proteins. Regulatory function of proteins

Plan:

1 Proteins involved in intercellular signaling
2 Receptor proteins
3 Intracellular regulatory proteins
- 3.1 Transcriptional regulator proteins
- 3.2 Translational regulation factors
- 3.3 splicing regulatory factors
- 3.4 Protein kinases and protein phosphatases

Introduction

Regulatory function of proteins— implementation by proteins of regulation of processes in a cell or in an organism, which is associated with their ability to receive and transmit information. The action of regulatory proteins is reversible and, as a rule, requires the presence of a ligand. More and more new regulatory proteins are constantly being discovered; at present, probably only a small part of them are known.

There are several types of proteins that perform a regulatory function:

proteins - receptors that perceive the signal
signal proteins - hormones and other substances that carry out intercellular signaling (many, although not all, of them are proteins or peptides)
regulatory proteins that regulate many processes within cells.

1. Proteins involved in intercellular signaling

Hormone proteins (and other proteins involved in intercellular signaling) affect metabolism and other physiological processes.

Hormones- substances that are formed in the endocrine glands, are carried by the blood and carry an information signal. Hormones spread randomly and act only on those cells that have suitable receptor proteins. Hormones bind to specific receptors. Hormones usually regulate slow processes, for example, the growth of individual tissues and the development of the body, but there are exceptions: for example, adrenaline (see the article adrenaline) is a stress hormone, a derivative of amino acids. It is released when a nerve impulse acts on the adrenal medulla. At the same time, the heart begins to beat more often, blood pressure rises and other responses occur. It also acts on the liver (breaks down glycogen). Glucose is released into the blood and is used by the brain and muscles as an energy source.

2. Receptor proteins

Receptor proteins can also be attributed to proteins with a regulatory function. Membrane proteins - receptors transmit a signal from the surface of the cell inward, transforming it. They regulate cell functions by binding to a ligand that "sat" on this receptor outside the cell; as a result, another protein inside the cell is activated.

Most hormones act on a cell only if there is a certain receptor on its membrane - another protein or glycoprotein. For example, β2-adrenergic receptor is located on the membrane of liver cells. Under stress, the adrenaline molecule binds to the β2-adrenergic receptor and activates it. The activated receptor then activates the G protein, which binds GTP. After many intermediate signal transduction steps, glycogen phosphorolysis occurs. The receptor performed the very first signal transduction operation leading to the breakdown of glycogen. Without it, there would be no subsequent reactions within the cell.

3. Intracellular regulatory proteins

Proteins regulate the processes occurring inside cells using several mechanisms:

interactions with DNA molecules (transcription factors)
by phosphorylation (protein kinase) or dephosphorylation (protein phosphatase) of other proteins
by interacting with the ribosome or RNA molecules (translation regulation factors)
effects on the process of intron removal (splicing regulatory factors)
influence on the rate of decay of other proteins (ubiquitins, etc.)

3.1. Transcriptional regulator proteins

transcription factor- this is a protein that, getting into the nucleus, regulates the transcription of DNA, that is, the reading of information from DNA to mRNA (mRNA synthesis according to the DNA template). Some transcription factors change the structure of chromatin, making it more accessible to RNA polymerases. There are various auxiliary transcription factors that create the desired DNA conformation for the subsequent action of other transcription factors. Another group of transcription factors are those factors that do not bind directly to DNA molecules, but are combined into more complex complexes using protein-protein interactions.

3.2. Translational regulation factors

Broadcast- synthesis of polypeptide chains of proteins according to the mRNA template, performed by ribosomes. Translation can be regulated in several ways, including with the help of repressor proteins that bind to mRNA. There are many cases where the repressor is the protein encoded by this mRNA. In this case, feedback regulation occurs (an example of this is the repression of the synthesis of the enzyme threonyl-tRNA synthetase).

3.3. splicing regulatory factors

Within eukaryotic genes, there are regions that do not code for amino acids. These regions are called introns. They are first transcribed into pre-mRNA during transcription, but then cut out by a special enzyme. This process of removal of introns, and then the subsequent stitching together of the ends of the remaining sections is called splicing (crosslinking, splicing). Splicing is carried out using small RNAs, usually associated with proteins, called splicing regulatory factors. Splicing involves proteins with enzymatic activity. They give the pre-mRNA the desired conformation. To assemble the complex (spliceosome), it is necessary to consume energy in the form of cleavable ATP molecules; therefore, this complex contains proteins with ATPase activity.

There is an alternative splicing. Splicing features are determined by proteins that are able to bind to the RNA molecule in the regions of introns or areas at the exon-intron border. These proteins can prevent the removal of some introns and at the same time promote the excision of others. Targeted regulation of splicing can have significant biological implications. For example, in the fruit fly Drosophila, alternative splicing underlies the sex determination mechanism.

3.4. Protein kinases and protein phosphatases

The most important role in the regulation of intracellular processes is played by protein kinases - enzymes that activate or inhibit the activity of other proteins by attaching phosphate groups to them.

Protein kinases regulate the activity of other proteins by phosphorylation - the addition of phosphoric acid residues to amino acid residues that have hydroxyl groups. Phosphorylation usually changes the functioning of the protein, such as enzymatic activity, as well as the position of the protein in the cell.

There are also protein phosphatases - proteins that cleave off phosphate groups. Protein kinases and protein phosphatases regulate metabolism as well as signaling within the cell. Phosphorylation and dephosphorylation of proteins is one of the main mechanisms of regulation of most intracellular processes.

G-protein activation cycle under the action of the receptor.

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This abstract is based on an article from the Russian Wikipedia. Synchronization completed 07/18/11 07:59:14
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REGULATORY PROTEINS

(from lat. regulo - put in order, adjust), a group of proteins involved in the regulation of decomp. biochem. processes. An important group of R. b., this article is devoted to the Crimea, are proteins that interact with DNA and control gene expression (gene expression in the signs and properties of the body). The vast majority of such R. would. operates at the level transcriptions(synthesis of messenger RNA, or mRNA, on a DNA template) and is responsible for the activation or repression (suppression) of mRNA synthesis (respectively, activator proteins and repressor proteins).

Known ca. 10 repressors. Naib. studied among them are prokaryotic repressors (bacteria, blue-green algae), which regulate the synthesis of enzymes involved in the metabolism of lactose (lac-repressor) in Escherichia coli (E. coli), and the bacteriophage A repressor. Their action is realized by binding to specific. sections of DNA (operators) of the corresponding genes and blocking the initiation of transcription of the mRNA encoded by these genes.

The repressor is usually a dimer of two identical polypeptide chains oriented in mutually opposite directions. Repressors physically impede RNA polymerase join the DNA in the promoter region (the binding site of the DNA-dependent RNA polymerase-enzyme that catalyzes the synthesis of mRNA on the DNA template) and start the synthesis of mRNA. It is assumed that the repressor only prevents transcription initiation and does not affect mRNA elongation.

The repressor can control synthesis to. - l. one protein or a number of proteins, the expression of which is coordinated. As a rule, these are serving one metabolic. path; their genes are part of one operon (a set of interconnected genes and adjacent regulatory regions).

Mn. repressors can exist both in active and inactive form, depending on whether or not they are associated with inducers or corepressors (respectively, substrates, in the presence of which specifically increases or decreases the rate of synthesis of a particular enzyme; see. Enzyme Regulators); these interactions have a non-covalent nature.

For efficient gene expression, it is necessary not only that the repressor be inactivated by the inducer, but also that the specific one be realized. positive turn-on signal, which is mediated by R. b., working "in pair" with cyclic. adenosine monophosphate (cAMP). The latter is associated with specific R. b. (the so-called CAP protein-activator of catabolite genes, or protein catabolism activator-BAC). This is a dimer with a pier. m. 45 thousand. After binding to cAMP, it acquires the ability to attach to specific. regions on DNA, sharply increasing the efficiency of transcription of the genes of the corresponding operon. At the same time, CAP does not affect the growth rate of the mRNA chain, but controls the stage of transcription initiation - the attachment of RNA polymerase to the promoter. In contrast to the repressor, CAP (in complex with cAMP) facilitates the binding of RNA polymerase to DNA and makes transcription initiation more frequent. The site of attachment of CAP to DNA adjoins directly to the promoter from the side opposite to that where the operator is localized.

Positive regulation (eg, E. coli lac operon) can be described by a simplified scheme: with a decrease in the concentration of glucose (the main carbon source), cAMP increases, which binds to SAR, and the resulting complex to the lac promoter. As a result, the binding of RNA polymerase to the promoter is stimulated and the rate of transcription of genes increases, to-rye encode, allowing the cell to switch to the use of another source of carbon-lactose. There are other special R. b. (eg, protein C), the functioning of which is described by a more complex scheme; they control a narrow range of genes and can act as both repressors and activators.

Repressors and operon-specific activators do not affect the specificity of the RNA polymerase itself. This last level of regulation is realized in cases involving massir. change in the spectrum of expressed genes. So, in E. coli, the genes encoding heat shock, which are expressed in a number of stressful conditions of the cell, are read by RNA polymerase only when a special R. b.-t is included in its class. called factor s 32 . The whole family of these R. b. (s-factors) that change the promoter specificity of RNA polymerase have been found in bacilli and other bacteria.

Dr. R.'s variety b. changes the catalytic Saint-va RNA polymerase (the so-called anti-terminator proteins). So, in bacteriophage X, two such proteins are known, to-rye modify RNA polymerase so that it does not obey cellular signals of termination (end) of transcription (this is necessary for the active expression of phage genes).

The general scheme of the genetic control, including the functioning of R. b., is also applicable to bacteria and eukaryotic cells (all organisms, with the exception of bacteria and blue-green algae).

Eukaryotic cells respond to ext. signals (for them, for example,) in principle, in the same way as bacterial cells react to changes in the concentration of nutrients. in-in in environment, i.e., by reversible repression or activation (derepression) of individual genes. At the same time, R. b., simultaneously controlling a large number genes, can be used in decomp. combinations. Similar combinational genetic regulation can provide differentiation. development of the entire complex multicellular organism due to the interaction. relatively small number of key R. b.

In the system of regulation of gene activity in eukaryotes, there is an addition. a level absent in bacteria, namely, the translation of all nucleosomes (repeating subunits chromatin), that are part of the transcription unit, into an active (decondensed) form in those cells where this one should be functionally active. It is assumed that a set of specific R. b. is involved here, which have no analogues in prokaryotes. These not only recognize specifics. sections of chromatin (or. DNA), but also cause certain structural changes in the adjacent areas. R., similar to activators and repressors of bacteria, apparently, participate in regulation of the subsequent transcription of separate genes in areas activir. chromatin.

Extensive class R. b. eukaryote- receptor proteins steroid hormones.

Amino acid sequence R. b. so-called encoded. regulatory genes. Mutational inactivation of the repressor leads to uncontrolled synthesis of mRNA, and, consequently, a certain protein (as a result translation- protein synthesis on an mRNA template). Such organisms are called constitutive mutants. The loss of the activator results in a persistent decrease in the synthesis of the regulated protein.

Lit.: Strayer L., Biochemistry, trans. from English, vol. 3, M., 1985, p. 112-25.

P. L. Ivanov.

Chemical encyclopedia. - M.: Soviet Encyclopedia. Ed. I. L. Knunyants. 1988 .

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PROTEINS, high-molecular organic compounds, biopolymers, built from 20 types of L a amino acid residues, connected in a certain sequence into long chains. The molecular weight of proteins varies from 5 thousand to 1 million. Name ... ... encyclopedic Dictionary

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Such as hormone receptors or the protein kinase regulatory subunit (an enzyme activated by cAMP) have activities that control the binding of regulatory ligands (ie, hormones and cAMP, respectively). In order for the activities of proteins of this class to be specifically regulated by ligands, such molecules must first of all have sites that specifically (and, as a rule, with high affinity) bind the ligand, which gives the molecules the ability to distinguish ligands from other chemical compounds. In addition, the protein must have such a structure that, as a result of ligand binding, its conformation can change, i.e. enable regulatory action. For example, in mammals, the specific binding of cAMP to the regulatory subunit of individual protein kinases results in a decrease in the binding affinity of this subunit to the catalytic subunit of the enzyme. This causes the dissociation of both protein subunits of the enzyme. The catalytic subunit, released from the inhibitory action of the regulatory subunit, is activated and catalyzes protein phosphorylation. Phosphorylation changes the properties of certain proteins, which affects the processes under the control of cAMP.

As for the group of hormones to which growth hormone belongs, the mRNA nucleotide sequence encoding their synthesis has been partially identified (Baxter J.D. ea, 1979). Each amino acid requires three nucleotides in DNA (and therefore in the mRNA transcribed from it). Although a given triplet of nucleotides (codon) corresponds to a given amino acid, there can be several codons for the same amino acid. This "degeneracy" of the genetic code makes it possible for the nucleotide sequences of the two given genes, which determine the structure of the two hormones, to be more or less homologous than is found in proteins. Thus, if two proteins share random amino acid sequence homology, then the sequences nucleic acids could show big differences. However, with respect to genes encoding the synthesis of hormones of the somatotropin group, this is not the case; the homology of the nucleic acid sequence is higher than the homology of the amino acid sequence (Baxter J.D. ea, 1979). Human growth hormone and chorionic somatomammotropin, which share 87% amino acid sequence homology, have 93% nucleic acid sequence homology in their mRNAs. Human and rat growth hormones share 70% amino acid sequence homology, and their mRNAs show 75% nucleic acid sequence homology. In some regions of the mRNA of rat growth hormone and human chorionic somatomammotropin (mRNA of two different hormones in two species), the homology is 85%. Thus, only minimal base changes in DNA cause hormone differences. Therefore, these data support the conclusion that the genes for these hormones evolved from a common ancestor. From the standpoint of the above ideas about symbols and the reactions they cause, it is significant that each of the three hormones in this group has an effect on growth. Growth hormone is a factor that determines linear growth. Prolactin plays an important role in the processes of lactation and thus ensures the growth of the newborn. Chorionic somatomammotropin, although its physiological significance has not been clearly established, can have a significant effect on intrauterine growth by directing nutrients entering the mother's body that affect fetal growth (

Proteins involved in the regulation of metabolism can themselves serve as ligands (for example, peptide hormones), i.e., interact with other proteins, such as hormone receptors, exerting a regulatory effect. Other regulatory proteins, such as hormone receptors or the protein kinase regulatory subunit (an enzyme activated by cAMP), have activities controlled by the binding of regulatory ligands (i.e., hormones and cAMP, respectively) (see Chapter 4). In order for the activities of proteins of this class to be specifically regulated by ligands, such molecules must first of all have sites that specifically (and, as a rule, with high affinity) bind the ligand, which gives the molecules the ability to distinguish the ligand from other chemical compounds. In addition, the protein must have such a structure that, as a result of ligand binding, its conformation can change, i.e., provide the possibility of exerting a regulatory action. For example, in mammals, specific binding of cAMP to the regulatory subunit of certain protein kinases results in a decrease in the binding affinity of this subunit to the catalytic subunit of the enzyme (see Chapter 4). This causes the dissociation of both protein subunits of the enzyme. The catalytic subunit, released from the inhibitory action of the regulatory subunit, is activated and catalyzes protein phosphorylation. Phosphorylation changes the properties of certain proteins, which affects the processes under the control of cAMP. The interaction of steroid hormones with their receptors causes such conformational changes in the latter that give them the ability to bind to the cell nucleus (see Chapter 4). This interaction also alters other receptor properties that are important in mediating the effect of steroid hormones on the transcription of certain types of mRNA.
In order to have such specialized and highly specific functions, proteins, as a result of the evolution of genes that determine their amino acid sequence, had to acquire the structure that they currently have. In some cases, other genes also take part in the process, encoding the synthesis of products that modify the regulatory proteins themselves (for example, by glycosylation). Since the evolution of genes, apparently, occurred due to such mechanisms as the mutation of pre-existing genes and the recombination of sections of different genes (as discussed), this imposed certain restrictions on the evolution of the protein. From an evolutionary point of view, it would probably be easier to modify the structures that are present than to create completely new genes. In this regard, the existence of some homology in the amino acid sequences of various proteins may not be unexpected, since their genes could have arisen as a result of the evolution of common precursors. Since, as noted above, protein regions adapted for binding regulatory ligands, such as cAMP and steroids or their analogs, must already have existed by the time these ligands appeared, it is easy to imagine how modification of the genes of such proteins can lead to the synthesis other proteins that retain high binding specificity of the regulatory ligand.
On fig. Figure 2-2 shows one of the hypothetical schemes for the evolution of primitive glucotransferase into three existing types of regulatory proteins: bacterial cAMP-binding protein (CAP or CRP), which regulates the transcription of several genes encoding enzymes that are involved in lactose metabolism, as well as A mammalian cAMP-binding protein that regulates the activity of cAMP-dependent protein kinase, which mediates the action of cAMP in humans (see Chapter 4), and adenylate cyclase (see Chapter 4). With regard to bacterial protein and kinase, the ATP-binding sites of primitive glucokinase have evolved towards acquiring greater cAMP binding specificity. The bacterial protein also acquired an additional polynucleotide (DNA)-binding capacity. The evolution of the kinase involves the acquisition of the glucophosphotransferase ability to phosphorylate proteins. Finally, adenylate cyclase could also be formed from glucokinase by replacing the ADP-generating function with a cAMP-generating one. These conclusions cannot but be purely hypothetical; nevertheless, they show how the molecular evolution of the enumerated regulatory proteins could have taken place.

Rice. 2-2. Proposed origin of cAMP-dependent protein kinase, adenylate cyclase, and bacterial cAMP-binding regulatory protein (Baxter, MacLeod).
Although many details in the picture of protein evolution are missing, currently available information about the structure of proteins and genes provides some basis for analyzing the question of whether the genes of some polypeptide hormones originated from a common precursor gene. Individual polypeptide hormones can be grouped according to their structural similarity. There is nothing surprising in the fact that hormones belonging to the same group may have similar physiological effects caused by them, as well as a similar mechanism of action. So, growth hormone (GH), prolactin and chorionic somatomammotropin (placental lactogen) are characterized by a high degree amino acid sequence homology. Glycoprotein hormones - thyrotropic hormone (TSH), human chorionic gonadotropin (hCG), follicle-stimulating (FSH) and luteinizing (LH) hormones - consist of two subunits, each, one of which (A-chain) is identical or almost identical for all hormones of a given groups. The amino acid sequence of the B subunits in various hormones, although not identical, has structural homology. It is these differences in B-chains that are likely to be of decisive importance for imparting specificity to the interaction of each hormone with its target tissue. Insulin shows some structural analogs and shares biological activity with other growth factors such as somatomedin and non-suppressed insulin-like activity (NIPA).
As for the group of hormones to which growth hormone belongs, the nucleotide sequence of the mRNA encoding their synthesis has been partially elucidated. Each amino acid requires three nucleotides in DNA (and hence in the mRNA transcribed from it). Although this triplet of nucleotides; (codon) corresponds to this particular amino acid, there can be several codons for the same amino acid. Such "degeneracy" of the genetic code makes it possible for the nucleotide sequences of the two given genes, which determine the structure of the two hormones, to be more or less homologous than is found in proteins. Thus, if two proteins share random amino acid sequence homology, then the nucleic acid sequences could show large differences. However, with respect to genes encoding the synthesis of hormones of the somatotropin group, this is not the case; nucleic acid sequence homology is higher than amino acid sequence homology. Human growth hormone and human chorionic somatomammotropin, which share 87% amino acid sequence homology, have 93% nucleic acid sequence homology in their mRNAs. Human and rat growth hormones share 70% amino acid sequence homology, and their mRNAs show 75% nucleic acid sequence homology. In some regions of the mRNA of rat growth hormone and human chorionic somatomammotropin (mRNA of two different hormones in two biological species), the homology is 85% (Fig. 2-3). Thus, only minimal base changes in DNA cause hormone differences. Therefore, these data support the conclusion that the genes for these hormones evolved from a common ancestor. From the standpoint of the above ideas about symbols and the reactions they cause, it is significant that each of the three hormones of this group has an effect on growth (see below). Growth hormone is a factor that determines linear growth. Prolactin plays an important role in the processes of lactation and thus ensures the growth of the newborn. Chorionic somatomammotropin, although its physiological significance has not been precisely established, can have a significant effect on intrauterine growth, directing nutrients entering the mother's body to fetal growth.

Rice. 2-3. Homology of amino acid (AA) sequences in rat growth hormone (GRH) and human chorionic somatomammotropin (human placental lactogen, PLC) and nucleic acid sequences in messenger RNA encoding the synthesis of these two hormones. The names of amino acids are abbreviated, as are the names of nucleic acids. The region corresponding to the amino acid sequence 134-149 is shown. Non-homologous nucleic acids and amino acids are underlined (Baxter et al.). U - uridine, C - cytosine, A - adenosine, G - guanosine.

The work of genes in any organism - prokaryotic, eukaryotic, unicellular or multicellular - is controlled and coordinated.

Different genes have different temporal activity. Some of them are characterized by constant activity. Such genes are responsible for the synthesis of proteins necessary for a cell or organism throughout life, for example, genes whose products are involved in the synthesis of ATP. Most of the genes have intermittent activity, they work only at certain moments when there is a need for their products - proteins. Genes also differ in their levels of activity (low or high).

Cell proteins are classified as regulatory and structural. Regulatory proteins synthesized on regulatory genes and control the work of structural genes. Structural genes encode structural proteins that perform structural, enzymatic, transport and other functions (except regulatory!).

Regulation of protein synthesis is carried out at all stages of this process: transcription, translation and post-translational modification, either by induction or by repression.

The regulation of gene activity in eukaryotic organisms is much more complicated than the regulation of prokaryotic gene expression, which is determined by the complexity of the organization of a eukaryotic organism, and especially a multicellular one. In 1961, French scientists F. Jacob, J. Monod and A. Lvov formulated a model of genetic control of the synthesis of proteins that catalyze the assimilation of lactose by the cell - the concept of an operon.

An operon is a group of genes controlled by a single regulator gene.

A regulator gene is a gene with constant low activity; a repressor protein is synthesized on it - a regulatory protein that can bind to an operator, inactivating it.

An operator is a starting point for reading genetic information; it controls the work of structural genes.

The structural genes of the lactose operon contain information about the enzymes involved in the metabolism of lactose. Therefore, lactose will serve as an inductor - an agent that initiates the work of the operon.

A promoter is the site of attachment for RNA polymerase.

The terminator is the site of termination of mRNA synthesis.

In the absence of an inductor, the system does not function, since the repressor "free" from the inductor - lactose - is connected to the operator. In this case, the RNA polymerase enzyme cannot catalyze the process of mRNA synthesis. If lactose (an inducer) is found in the cell, it, interacting with the repressor, changes its structure, as a result of which the repressor releases the operator. RNA polymerase binds to the promoter, mRNA synthesis begins (transcription of structural genes). Then proteins are formed on the ribosomes according to the program of the mRNA-lactose operon. In prokaryotic organisms, one mRNA molecule rewrites information from all the structural genes of the operon, i.e. An operon is a transcription unit. Transcription continues as long as lactose molecules remain in the cytoplasm of the cell. As soon as all the molecules are processed by the cell, the repressor closes the operator, and mRNA synthesis stops.

Thus, mRNA synthesis and, accordingly, protein synthesis must be strictly regulated, since the cell does not have enough resources for simultaneous transcription and translation of all structural genes. Both pro- and eukaryotes constantly synthesize only those mRNAs that are necessary to perform basic cellular functions. The expression of other structural genes is carried out under the strict control of regulatory systems that trigger transcription only when there is a need for a certain protein (proteins).

REGULATORY PROTEINS (from lat. regulo - put in order, adjust), a group of proteins. involved in the regulation of decomp. biochem. processes. An important group of regulatory proteins, which this article is devoted to, are proteins that interact with DNA and control gene expression (gene expression in the characteristics and properties of an organism). The vast majority of these regulatory proteins function at the level of transcription (synthesis of messenger RNA, or mRNA, on a DNA template) and are responsible for the activation or repression (suppression) of mRNA synthesis (activator proteins and repressor proteins, respectively).

The repressor is usually a dimer of two identical polypeptide chains oriented in mutually opposite directions. Repressors physically prevent RNA polymerase from attaching to DNA at the promoter site (the site of binding of the DNA-dependent RNA polymerase-enzyme that catalyzes mRNA synthesis on the DNA template) and from starting mRNA synthesis. It is assumed that the repressor only prevents transcription initiation and does not affect mRNA elongation.

The repressor can control synthesis to. - l. a single protein or a range of proteins. whose expression is coordinated. As a rule, these are enzymes serving one metabolic. path; their genes are part of one operon (a set of interconnected genes and adjacent regulatory regions).

Mn. repressors can exist in both active and inactive forms, depending on whether or not they are associated with inducers or corepressors (respectively, substrates in the presence of which the rate of synthesis of a particular enzyme is specifically increased or decreased; see Enzyme Regulators); these interactions have a non-covalent nature.

For efficient gene expression, it is necessary not only that the repressor be inactivated by the inducer, but also that the specific one be realized. positive turn-on signal, which is mediated by regulatory proteins working "in pair" with cyclic. adenosine monophosphate (cAMP). The latter binds to specific regulatory proteins (the so-called CAP-protein-activator of catabolite genes, or proteins. activator of catabolism-BAC). This is a dimer with a pier. m. 45 thousand. After binding to cAMP, it acquires the ability to attach to specific. regions on DNA, sharply increasing the efficiency of transcription of the genes of the corresponding operon. At the same time, CAP does not affect the growth rate of the mRNA chain, but controls the stage of transcription initiation - the attachment of RNA polymerase to the promoter. In contrast to the repressor, CAP (in complex with cAMP) facilitates the binding of RNA polymerase to DNA and makes transcription initiation more frequent. The site of attachment of CAP to DNA adjoins directly to the promoter from the side opposite to that where the operator is localized.

Positive regulation (eg, of the E. coli lac operon) can be described in a simplified way: with a decrease in the concentration of glucose (the main carbon source), the concentration of cAMP, which binds to CAP, increases, and the resulting complex increases with the lac promoter. As a result, the binding of RNA polymerase to the promoter is stimulated and the rate of transcription of genes that encode enzymes that allow the cell to switch to another carbon source, lactose, increases. There are other special regulatory proteins (eg, protein C), the functioning of which is described by a more complex scheme; they control a narrow range of genes and can act as both repressors and activators.

Repressors and operon-specific activators do not affect the specificity of the RNA polymerase itself. This last level of regulation is realized in cases involving massir. change in the spectrum of expressed genes. So, in E. coli, the genes encoding heat shock proteins, which are expressed in a number of stressful conditions of the cell, are read by RNA polymerase only when a special regulatory protein, the so-called. factor s32. A whole family of these regulatory proteins (s-factors), which change the promoter specificity of RNA polymerase, have been found in bacilli and other bacteria.

Dr. a variety of regulatory proteins changes catalytic. properties of RNA polymerase (the so-called anti-terminator proteins). For example, in bacteriophage X, two such proteins are known that modify RNA polymerase so that it does not obey the cellular signals of termination (end) of transcription (this is necessary for the active expression of phage genes).

The general scheme of the genetic control, including the functioning of regulatory proteins, is also applicable to bacteria and eukaryotic cells (all organisms except bacteria and blue-green algae).

Eukaryotic cells respond to ext. signals (for them, for example, hormones) in principle, in the same way as bacterial cells react to changes in the concentration of nutrients. substances in the environment, i.e. by reversible repression or activation (derepression) of individual genes. At the same time, regulatory proteins that simultaneously control the activity of a large number of genes can be used in decomp. combinations. Similar combinational genetic regulation can provide differentiation. development of the entire complex multicellular organism due to the interaction. relatively few key regulatory proteins

In the system of regulation of gene activity in eukaryotes, there is an addition. a level absent in bacteria, namely, the translation of all nucleosomes (repeating chromatin subunits) that make up the transcription unit into an active (decondensed) form in those cells where this gene should be functionally active. It is assumed that a set of specific regulatory proteins that have no analogues in prokaryotes are involved here. These proteins not only recognize specific sections of chromatin (or. DNA), but also cause certain structural changes in the adjacent areas. regulatory proteins like activators and repressors of bacteria, apparently, are involved in the regulation of the subsequent transcription of individual genes in areas activir. chromatin.

An extensive class of regulatory proteins eukaryotic receptor proteins of steroid hormones.

The amino acid sequence of regulatory proteins is encoded by the so-called. regulatory genes. Mutational inactivation of the repressor leads to uncontrolled synthesis of mRNA, and, consequently, of a certain protein (as a result of translation-protein synthesis on the mRNA template). Such organisms are called constitutive mutants. The loss of the activator as a result of mutation leads to a persistent decrease in the synthesis of the regulated protein.