Classification of proteins by structure

- Fibrillar – the most important is the secondary structure (the tertiary structure is almost or not expressed at all), insoluble in water, and characterized by great mechanical strength. Long parallel polypeptide chains held together by cross-links form long fibers or layered structures. They perform structural functions in cells and in the body, for example, they are part of connective tissue. This group includes collagen (tendons, intercellular substance of bone tissue), myosin (muscle sarcomeres), fibroin (silk, spider web), keratin (hair, horns, nails, feathers).

- Globular– the tertiary structure is most important. Polypeptide chains are folded into compact globules. Soluble. Easily form colloidal suspensions. They perform the function of enzymes, antibodies (serum globulins determine immunological activity) and in some cases hormones (for example, insulin). They play an important role in protoplasm, retaining water and some other substances in it and helping to maintain molecular organization.

- Intermediate– fibrillar in nature, but soluble. An example is fibrinogen, which is converted into insoluble fibrin during blood clotting.

Functions of proteins:

1. Enzymatic

2. Proteins-hormones

3.Regulatory

4. Protective

5. Transport

6. Structural proteins

7. Contractile proteins

8. Receptor proteins

9. Toxin proteins

10. Proteins are enzyme inhibitors

11. Proteins of the inner membranes.

Nucleic acids

-irregular heteropolymers whose monomers are nucleotides.

Nucleic acids were first isolated in 1869 by the Swedish biochemist Friedrich Miescher from pus cells. There are 2 types of nucleic acids: deoxyribonucleic acid and ribonucleic acid or DNA and RNA. Nucleotides, which are monomers of nucleic acids, do not have a simple structure.

Nucleic acids contain nitrogenous bases, five-carbon sugars, and a phosphoric acid residue.

There can be 2 types of pentoses in the composition of nucleic acids: in DNA - deoxyribose, in RNA - ribose. Nucleic acids are named after the pentose they contain.

The nitrogenous bases in nucleic acids are called adenine, guanine, thymine, cytosine and uracil, they are presented in the figure below.

Nucleotides are monomers of nucleic acids. In addition to the mentioned nucleotides, more than 20 “minor” nucleotides are found in small quantities in nucleic acids - their nitrogenous bases are derivatives of 5 main ones.

The formation of nucleotides occurs in 2 stages. 1) Pentose, combining with a nitrogenous base during a condensation reaction, forms nucleoside

2) As part of another condensation reaction, a phosphoric acid residue is added to the nucleoside to form a phosphorus-ester bond.

3) The nucleotides are connected to each other through a condensation reaction, and a phosphodiester bond is formed between the 3" hydroxyl of one hydroxide residue and the 5" hydroxyl of the other. The bond formed in this case is called phosphodiester. The phosphodiester bonds in the polynucleotide chain are covalent, strong, and stable.

Sugars together with a nitrogenous base are called nucleosides (adenosine, guanosine, thymidine, cytidine). If a 1-, 2-, or 3-phosphorus residue is attached to them, then this entire structure is called, respectively, a nucleotide monophosphate, diphosphate or triphosphate or nucleotide (adenine, guanine, thymine, cytosine).

This is what the ATP model looks like in space.

The polynucleotide chain has 2 ends: 3" end, where 3" is not connected to anything (pentose hydroxy); 5" - pentose hydroxyl is associated only with phosphate. It is customary to consider the 5" terminal nucleotide to be the beginning of the chain, and the 3" - its end. In the body, the breakdown of polypeptide chains occurs under the action of enzymes nucleases.

The nitrogenous base that makes up DNA is divided into two groups - pyrimidine and purine. DNA contains adenine, thymine, cytosine and guanine, and RNA contains uracil instead of thymine. As you know, DNA is a large archive in which information is stored, and RNA is a molecule that transfers information from the nucleus to the cytoplasm for the synthesis of proteins. With differences in function are differences in structure. RNA is more chemically active due to the fact that its sugar, ribose, contains a hydroxyl group, while deoxyribose does not have oxygen. Due to the lack of oxygen, DNA is more inert, which is important for its function of storing information so that it does not undergo any reactions.

In the early 50s, the American biochemist Edwin Chargaff studied the nucleotide composition of DNA; he summarized the results of his experiments in the form of rules (Chargaff’s rules)

It has been established that the diameter of a DNA molecule is 2 nanometers, there are 10 nucleotides per 1 full turn of the helix in each chain, and the internucleotide distance along the helix axis is 0.34 nanometers.

The complete decoding of the structure of DNA was made in 1953 by the American biochemist James Watson and the English physicist Francis Crick. Working together at the University of Cambridge, they used all the data known at that time:

Watson and Crick DNA model:

For a long time it was believed that there was only the form of DNA that was described by Watson and Crick, but it is now known that DNA can form more than 10 different forms, capable of intertransition and which differ from each other in a number of parameters. For example: by the number of pairs of nucleotide residues in a turn (spiral pitch). For example:

A - shape - helix pitch 10 base pairs;

B - shape - helix pitch 10 base pairs.

C - form - 9.3 base pairs

Z - shape - 12 base pairs.

All shapes except Z are right-handed; Z - left-handed shape. Quantitatively, the B form predominates in cells.

DNA molecules - eukaryotes and many viruses exist in linear forms, DNA - bacterial cells, chloroplasts, mitochondria, some viruses have a ring shape. The DNA of some viruses is single-stranded.

Eukaryotic DNA is associated with proteins and forms the main substance of the nucleus - chromitin.

Properties of DNA

The substance is white in color, fibrous structure, poorly soluble in water, dissolves in strong saline solutions. DNA solutions are highly viscous and birefringent. Molecules are optically and electrically active. They firmly bind multivalent metal ions and undergo alkylation and deamination reactions of nitrogenous bases.

Squirrels

– biopolymers, the monomers of which are α-amino acids linked to each other by peptide bonds.
Isolates amino acids hydrophobic And hydrophilic, which, in turn, are divided into acidic, basic and neutral. A feature of a-amino acids is their ability to interact with each other to form peptides.
Highlight:

1. dipeptides (carnosine and anserine, localized in mitochondria; being AO, preventing their swelling);

2. oligopeptides, including up to 10 amino acid residues. For example: tripeptide glutathione serves as one of the main reducing agents in ARZ, which regulates the intensity of LPO. Vasopressin And oxytocin- hormones of the posterior lobe of the pituitary gland, include 9 amino acids.

Exist polypeptide s and, depending on the properties they exhibit, they are classified into different classes of compounds. Doctors believe that if parenteral administration of a polypeptide causes rejection (allergic reaction), then it should be considered protein; if such a phenomenon is not observed, then the term remains the same ( polypeptide). Adenohypophysis hormone ACTH, affecting the secretion of GCS in the adrenal cortex, are classified as polypeptides (39 amino acids), and insulin, consisting of 51 monomers and capable of triggering an immune response, is a protein.

Levels of organization of a protein molecule.

Any polymer tends to adopt a more energetically favorable conformation, which is maintained due to the formation of additional bonds, which is carried out using groups of amino acid radicals. It is customary to distinguish four levels of structural organization of proteins. Primary structure– sequence of amino acids in a polypeptide chain, covalently linked by peptide ( amide) bonds, and neighboring radicals are at an angle of 180 0 (trans-form). The presence of more than 2 dozen different proteinogenic amino acids and their ability to bind in different sequences determines the diversity of proteins in nature and their performance of a wide variety of functions. The primary structure of the proteins of an individual person is genetically determined and transmitted from parents using DNA and RNA polynucleotides. Depending on the nature of the radicals and with the help of special proteins - chaperones the synthesized polypeptide chain fits in space - protein folding.

Secondary structure The protein has the form of a helix or a β-pleated layer. Fibrillar proteins (collagen, elastin) have beta structure. The alternation of helical and amorphous (disordered) sections allows them to come closer and, with the help of chaperones, form a more densely packed molecule - tertiary structure.

The combination of several polypeptide chains in space and the creation of a functional macromolecular formation forms quaternary structure squirrel. Such micelles are usually called oligo- or multimers, and their components are subunits ( protomers). A protein with a quaternary structure has biological activity only if all its subunits are connected to each other.

Thus, any natural protein is characterized by a unique organization, which ensures its physicochemical, biological and physiological functions.

Physicochemical characteristics.

Proteins are large in size and have a high molecular weight, which ranges from 6,000 to 1,000,000 Daltons and higher, depending on the number of amino acids and the number of protomers. Their molecules have different forms: fibrillar– it retains the secondary structure; globular– having a higher organization; and mixed. The solubility of proteins depends on the size and shape of the molecule and on the nature of amino acid radicals. Globular proteins are highly soluble in water, while fibrillar proteins are either slightly or insoluble.

Properties of protein solutions: have low osmotic but high oncotic pressure; high viscosity; poor diffusion ability; often cloudy; opalescent ( Tyndall phenomenon), - all this is used in the isolation, purification, and study of native proteins. The separation of the components of a biological mixture is based on their precipitation. Reversible deposition is called salting out , developing under the action of alkali metal salts, ammonium salts, dilute alkalis and acids. It is used to obtain pure fractions that retain their native structure and properties.

The degree of ionization of a protein molecule and its stability in solution are determined by the pH of the medium. The pH value of a solution at which the particle charge tends to zero is called isoelectric point . Such molecules are capable of moving in an electric field; the speed of movement is directly proportional to the amount of charge and inversely proportional to the mass of the globule, which underlies electrophoresis for the separation of serum proteins.

Irreversible deposition - denaturation. If the reagent penetrates deep into the micelle and destroys additional bonds, the compactly laid thread unfolds. Due to the released groups, approaching molecules stick together and precipitate or float and lose their biological properties. Denaturing factors: physical(temperature above 40 0, various types of radiation: X-ray, α-, β-, γ, UV); chemical(concentrated acids, alkalis, heavy metal salts, urea, alkaloids, some drugs, poisons). Denaturation is used in asepsis and antiseptics, as well as in biochemical research.

Proteins have different properties (Table 1.1).

Table 1.1

Biological properties of proteins

Protein classification

Highlight simple proteins , consisting only of amino acids, and complex , including prosthetic group. Simple proteins are divided into globular and fibrillar, and also depending on the amino acid composition on basic, acidic, neutral. Globular basic proteins - protamines and histones. They have a low molecular weight, due to the presence of arginine and lysine they have a pronounced basicity, due to the “-” charge, they easily interact with polyanions of nucleic acids. Histones, by binding to DNA, help compactly fit into the nucleus and regulate protein synthesis. This fraction is heterogeneous and when interacting with each other, they form nucleosomes, on which DNA strands are wound.

Acid globular proteins include albumins and globulins, contained in extracellular fluids (blood plasma, cerebrospinal fluid, lymph, milk) and differing in weight and size. Albumins have a molecular weight of 40-70 thousand D, in contrast to globulins (over 100 thousand D). The former include glutamic acid, which creates a large “-” charge and a hydration shell, allowing their solution to be highly stable. Globulins are less acidic proteins, therefore they are easily salted out and are heterogeneous; they are divided into fractions using electrophoresis. They are able to bind to various compounds (hormones, vitamins, poisons, drugs, ions), providing their transport. With their help, important parameters of homeostasis are stabilized: pH and oncotic pressure. Also distinguished immunoglobulins(IgA, IgM, IgD, IgE, IgG), which serve as antibodies, as well as protein coagulation factors.

The clinic uses the so-called protein ratio (BC) , representing the ratio of albumin concentration to globulin concentration:

Its values ​​fluctuate depending on pathological processes.

Fibrillar proteins divided into two groups: soluble ( actin, myosin, fibrinogen) and insoluble in water and water-salt solutions (support proteins - collagen, elastin, reticulin and integumentary ones - keratin fabrics).

The classification of complex proteins is based on the structural features of the prosthetic group. Metalloprotein — ferritin, rich in iron cations, and localized in the cells of the mononuclear phagocyte system (hepatocytes, splenocytes, bone marrow cells), is a depot of this metal. Excess iron leads to accumulation in tissues - hemosiderin, provoking development hemosiderosis. Metalloglycoproteins - transferrin And ceruloplasmin blood plasma, serving as transport forms of iron and copper ions, respectively, their antioxidant activity was revealed. The work of many enzymes depends on the presence of metal ions in the molecules: for xanthine dehydrogenase - Mo ++, arginase - Mn ++, and alcoholDH - Zn ++.

Phosphoproteins – milk caseinogen, yolk vitellin and egg white ovalbumin, fish caviar ichthulin. They play an important role in the development of the embryo, fetus, and newborn: their amino acids are necessary for the synthesis of their own tissue proteins, and phosphate is used either as a link in PL - the obligatory structures of cell membranes, or as an important component of macroergs - energy sources in the genesis of various compounds. Enzymes regulate their activity through phosphorylation-dephosphorylation.

Part nucleoproteins includes DNA and RNA. Histones or protamines act as apoproteins. Any chromosome is a complex of one DNA molecule with many histones. By using nucleosomes the thread of this polynucleotide is wound, which reduces its volume.

Glycoproteins include various carbohydrates (oligosaccharides, GAGs such as hyaluronic acid, chondroitin-, dermatan-, keratan-, heparan sulfates). Mucus, rich in glycoproteins, has a high viscosity, protecting the walls of hollow organs from irritants. Membrane glycoproteins provide intercellular contacts, the functioning of receptors, and in the plasma membranes of erythrocytes they are responsible for the group specificity of blood. Antibodies (oligosaccharides) interact with specific antigens. The functioning of interferons and the complement system is based on the same principle. Ceruloplasmin and transferrin, which transport copper and iron ions in the blood plasma, are also glycoproteins. Some hormones of the adenohypophysis belong to this class of proteins.

Lipoproteins the prosthetic group contains various lipids (TAG, free cholesterol, its esters, PL). Despite the presence of a wide variety of substances, the structural principle of drug micelles is similar (Fig. 1.1). Inside this particle there is a fat droplet containing non-polar lipids: TAG and cholesterol esters. Outside, the nucleus is surrounded by a single-layer membrane formed by PL, a protein (apolipoprotein) and HS. Some proteins are integral and cannot be separated from the lipoprotein, while others are able to be transferred from one complex to another. Polypeptide fragments form the structure of the particle, interact with receptors on the surface of cells, determining which tissues need it, and serve as enzymes or their activators that modify the drug. The following types of lipoproteins were isolated by ultracentrifugation: CM, VLDL, LPPP, LDL, HDL. Each type of lipid is formed in different tissues and ensures the transport of certain lipids in biological fluids. The molecules of these proteins are highly soluble in the blood, because They are small in size and have a negative charge on the surface. Part of the LP can easily diffuse through the intima of the arteries, nourishing it. Chylomicrons serve as carriers of exogenous lipids, moving first through the lymph and then through the bloodstream. As they progress, CMs lose their lipids, giving them to the cells. VLDL serve as the main transport forms of lipids synthesized in the liver, mainly TAG, and the delivery of endogenous cholesterol from hepatocytes to organs and tissues is carried out LDL. As they donate lipids to target cells, their density increases (they are converted into BOB). The catabolic phase of cholesterol metabolism occurs HDL, which transfer it from tissues to the liver, from where it is excreted through the gastrointestinal tract from the body as part of bile.

U chromoproteins a prosthetic group can be a substance that has a color. Subclass - hemoproteins, serves as the non-protein part heme. Hemoglobin erythrocytes ensure gas exchange, have a quaternary structure, and consist of 4 different polypeptide chains in the embryo, fetus, and child (Section IV. Chapter 1). Unlike Hb myoglobin has one heme and one polypeptide chain, rolled into a globule. Myoglobin's affinity for oxygen is higher than that of hemoglobin, so it is able to accept the gas, store it and release it to the mitochondria as needed. Heme-containing proteins include catalase, peroxidase, which are ARZ enzymes; cytochromes– components of the ETC, which is responsible for the main bioenergetic process in cells. Among the dehydrogenases involved in tissue respiration, we find flavoproteins- chromoproteins that have a yellow (flavos - yellow) color due to the presence of flavonoids - components FMN and FAD. Rhodopsin– a complex protein whose prosthetic group is the active form of vitamin A – retinol yellow-orange color. Visual purple is the main light-sensitive substance of the rods of the retina and ensures the perception of light at dusk.

Functions of proteins

There are several approaches to classifying proteins: by the shape of the protein molecule, by the composition of the protein, by function. Let's look at them.

Classification according to the shape of protein molecules

Based on the shape of protein molecules, they are distinguished fibrillar proteins and globular proteins.

Fibrillar proteins are long thread-like molecules, the polypeptide chains of which are elongated along one axis and linked to each other by cross-links (Fig. 18b). These proteins are characterized by high mechanical strength and are insoluble in water. They perform mainly structural functions: they are part of tendons and ligaments (collagen, elastin), form silk and spider web fibers (fibroin), hair, nails, feathers (keratin).

In globular proteins, one or more polypeptide chains are folded into a dense compact structure - a coil (Fig. 18a). These proteins are generally highly soluble in water. Their functions are varied. Thanks to them, many biological processes are carried out, which will be discussed in more detail below.

Rice. 18. Shape of protein molecules:

a – globular protein, b – fibrillar protein

Classification according to the composition of the protein molecule

Proteins can be divided into two groups according to their composition: simple And complex proteins. Simple proteins consist only of amino acid residues and do not contain other chemical components. Complex proteins, in addition to polypeptide chains, contain other chemical components.

Simple proteins include RNase and many other enzymes. The fibrillar proteins collagen, keratin, and elastin are simple in composition. Plant storage proteins contained in cereal seeds - glutelins, And histones– proteins that form the chromatin structure also belong to simple proteins.

Among complex proteins there are metalloproteins, chromoproteins, phosphoproteins, glycoproteins, lipoproteins etc. Let us consider these groups of proteins in more detail.

Metalloproteins

Metalloproteins include proteins that contain metal ions. Their molecules contain metals such as copper, iron, zinc, molybdenum, manganese, etc. Some enzymes are metalloproteins by nature.

Chromoproteins

Chromoproteins contain colored compounds as a prosthetic group. Typical chromoproteins are the visual protein rhodopsin, which takes part in the process of light perception, and the blood protein hemoglobin (Hb), the quaternary structure of which was discussed in the previous paragraph. Hemoglobin contains heme, which is a flat molecule in the center of which the Fe 2+ ion is located (Fig. 19). When hemoglobin interacts with oxygen, it forms oxyhemoglobin. In the alveoli of the lungs, hemoglobin is saturated with oxygen. In tissues where the oxygen content is low, oxyhemoglobin breaks down releasing oxygen, which is used by cells:

.

Hemoglobin can form a compound with carbon (II) monoxide called carboxyhemoglobin:

.

Carboxyhemoglobin is not able to attach oxygen. This is why carbon monoxide poisoning occurs.

Hemoglobin and other heme-containing proteins (myoglobin, cytochromes) are also called hemoproteins due to the presence of heme in their composition (Fig. 19).

Rice. 19. Heme

Phosphoproteins

Phosphoproteins contain phosphoric acid residues connected to the hydroxyl group of amino acid residues by an ester bond (Fig. 20).

Rice. 20. Phosphoprotein

Milk protein casein is a phosphoprotein. It contains not only phosphoric acid residues, but also calcium ions. Phosphorus and calcium are necessary for the growing body in large quantities, in particular for the formation of the skeleton. In addition to casein, there are many other phosphoproteins in cells. Phosphoproteins can undergo dephosphorylation, i.e. lose a phosphate group:

phosphoprotein + H 2 protein + H 3 PO 4

Dephosphorylated proteins can, under certain conditions, be phosphorylated again. Their biological activity depends on the presence of a phosphate group in their molecule. Some proteins exhibit their biological function in a phosphorylated form, others in a dephosphorylated form. Many biological processes are regulated through phosphorylation and dephosphorylation.

Lipoproteins

Lipoproteins include proteins containing covalently bound lipids. These proteins are found in cell membranes. The lipid (hydrophobic) component holds the protein in the membrane (Fig. 21).

Rice. 21. Lipoproteins in the cell membrane

Lipoproteins also include blood proteins that participate in the transport of lipids and do not form a covalent bond with them.

Glycoproteins

Glycoproteins contain a covalently linked carbohydrate component as a prosthetic group. Glycoproteins are divided into true glycoproteins And proteoglycans. The carbohydrate groups of true glycoproteins usually contain up to 15–20 monosaccharide components; in proteoglycans they are built from a very large number of monosaccharide residues (Fig. 22).

Rice. 22. Glycoproteins

Glycoproteins are widely distributed in nature. They are found in secretions (saliva, etc.), as part of cell membranes, cell walls, intercellular substance, connective tissue, etc. Many enzymes and transport proteins are glycoproteins.

Classification by function

According to the functions they perform, proteins can be divided into structural, nutritional and storage proteins, contractile, transport, catalytic, protective, receptor, regulatory, etc.

Structural proteins

Structural proteins include collagen, elastin, keratin, fibroin. Proteins take part in the formation of cell membranes, in particular, they can form channels in them or perform other functions (Fig. 23).

Rice. 23. Cell membrane.

Nutrient and storage proteins

Nutrient protein is casein, the main function of which is to provide the growing body with amino acids, phosphorus and calcium. Storage proteins include egg whites and plant seed proteins. These proteins are consumed during embryo development. In the human and animal bodies, proteins are not stored in reserve; they must be systematically supplied with food, otherwise dystrophy may develop.

Contractile proteins

Contractile proteins ensure muscle function, movement of flagella and cilia in protozoa, changes in cell shape, and movement of organelles within the cell. These proteins are myosin and actin. These proteins are not only present in muscle cells; they can be found in cells of almost any animal tissue.

Transport proteins

Hemoglobin, discussed at the beginning of the paragraph, is a classic example of a transport protein. There are other proteins in the blood that provide transport of lipids, hormones and other substances. Cell membranes contain proteins that can transport glucose, amino acids, ions and some other substances across the membrane. In Fig. Figure 24 schematically shows the operation of a glucose transporter.

Rice. 24. Transport of glucose across the cell membrane

Enzyme proteins

Catalytic proteins, or enzymes, are the most diverse group of proteins. Almost all chemical reactions occurring in the body occur with the participation of enzymes. To date, several thousand enzymes have been discovered. They will be discussed in more detail in the following paragraphs.

Protective proteins

This group includes proteins that protect the body from invasion by other organisms or protect it from damage. Immunoglobulins, or antibodies, are able to recognize bacteria, viruses or foreign proteins that have entered the body, bind to them and contribute to their neutralization.

Other blood components, thrombin and fibrinogen, play important roles in the blood clotting process. They protect the body from blood loss when blood vessels are damaged. Under the influence of thrombin, fragments of the polypeptide chain are split off from fibrinogen molecules, resulting in the formation fibrin:

fibrinogen fibrin.

The resulting fibrin molecules aggregate, forming long insoluble chains. The blood clot is initially loose, then it is stabilized by interchain cross-links. In total, about 20 proteins are involved in the blood clotting process. Disturbances in the structure of their genes cause diseases such as hemophilia– decreased blood clotting.

Receptor proteins

The cell membrane is an obstacle to many molecules, including molecules intended to transmit signals inside cells. Nevertheless, the cell is capable of receiving signals from the outside due to the presence of special structures on its surface. receptors many of which are proteins. A signaling molecule, for example, a hormone, interacting with a receptor forms a hormone-receptor complex, the signal from which is transmitted further, as a rule, to a protein intermediary. The latter triggers a series of chemical reactions, the result of which is the biological response of the cell to the influence of an external signal (Fig. 25).

Fig.25. Transmission of external signals into the cell

Regulatory proteins

Proteins involved in the control of biological processes are classified as regulatory proteins. Some of them belong to hormones. Insulin And glucagon regulate blood glucose levels. Growth hormone, which determines body size, and parathyroid hormone, which regulates the exchange of phosphates and calcium ions, are regulatory proteins. This class of proteins also includes other proteins involved in the regulation of metabolism.

Interesting to know! The plasma of some Antarctic fish contains proteins with antifreeze properties that protect the fish from freezing, and in a number of insects, in the places where the wings are attached, there is a protein called resilin, which has almost perfect elasticity. One of the African plants synthesizes the protein monellin with a very sweet taste.

Based on differences in composition or form.

By composition Proteins are divided into two groups:

Simple proteins (proteins) consist only of amino acids: protamines and histones have basic properties and are part of nucleoproteins. Histones are involved in the regulation of genome activity. Prolamins and glutelins are proteins of plant origin that make up the bulk of gluten. Albumins and globulins are proteins of animal origin. Blood serum, milk, egg whites, and muscles are rich in them.

Complex proteins (proteids = proteins) contain a non-protein part - a prosthetic group. If the prosthetic group is a pigment (hemoglobin, cytochromes), then these are chromoproteins. Proteins associated with nucleic acids are nucleoproteins.

Lipoproteins are associated with some lipid. Phosphoproteins - consist of protein and labile phosphate. There are many of them in milk, in the central nervous system, and fish eggs. Glycoproteins are associated with carbohydrates and their derivatives.

Metalloproteins are proteins that contain non-heme iron and also form coordination lattices with metal atoms in enzyme proteins.

They are distinguished by shape

Globular proteins are tightly folded polypeptide chains of spherical shape; tertiary structure is important for them. Well soluble in water, in dilute solutions of acids, bases, salts. Globular proteins perform dynamic functions. For example, insulin, blood proteins, enzymes.

Fibrillar proteins are molecules of secondary structure. They are built from parallel, relatively highly stretched peptide chains, elongated, collected in bundles, forming fibers (keratin of nails, hair, cobwebs, silk, tendon collagen). They perform a predominantly structural function.

Functions of proteins:

Regulatory function - take part in the regulation of metabolism. Hormones affect the activity of enzymes, slowing down or accelerating metabolic processes, changing the permeability of cell membranes, maintaining a constant concentration of substances in the blood and cells, and participating in the growth process. The hormone insulin regulates blood sugar levels by increasing the permeability of cell membranes to glucose, promotes glycogen synthesis, and increases the formation of fats from carbohydrates.

Protective function = Immunological. In response to the penetration of foreign proteins or microorganisms (antigens) into the body, special proteins are formed - antibodies that can bind and neutralize them. The synthesis of immunoglobulins occurs in lymphocytes. Fibrin, formed from fibrinogen, helps stop bleeding.

Motor function. Contractile proteins ensure the movement of cells and intracellular structures: the formation of pseudopodia, the flickering of cilia, the beating of flagella, muscle contraction, and the movement of leaves in plants.

Signal function. The surface membrane of the cell contains embedded protein molecules that can change their tertiary structure in response to environmental factors. This is how signals are received from the external environment and commands are transmitted to the cell.

Storage function. Some substances may be stored in the body. For example, during the breakdown of hemoglobin, iron is not removed from the body, but is stored in the spleen, forming a complex with the protein ferritin. Spare proteins include egg and milk proteins.

Energy function. When 1 g of protein breaks down into final products, 17.6 kJ is released. The breakdown occurs first to amino acids, and then to water, ammonia and carbon dioxide.

However, proteins are used as a source of energy when fats and carbohydrates are used up.

Catalytic function. Acceleration of biochemical reactions under the influence of proteins - enzymes.

Trophic.

They nourish the embryo in the early stages of development and store biologically valuable substances and ions.

The complexity of the structure of protein molecules and the extreme diversity of their functions make it extremely difficult to create a single clear classification of them on any one basis. Proteins can be classified according to their composition (simple, complex), structure (fibrillar, globular, intermediate), and functions. Let's take a closer look at the structural classification.

Fibrillar proteins are highly elongated (secondary structure is most important) and perform structural functions.

Globular proteins, which can be roughly represented in the form of spheres (the most important is the tertiary structure), take part in such specific processes as catalysis, transport, regulation.

In addition to the types of proteins listed above, the body contains small or low-carbon polypeptides, which may not themselves have a fixed structure, but acquire it when interacting with other macromolecules. It should be noted that this classification cannot claim to be complete, since there are proteins that do not belong to any of these classes. For example, myosin, which in its structure contains characteristics of both fibrillar and globular proteins.

A protein with the original, natural chain arrangement, i.e., having a three-dimensional configuration, is called native, a protein with an unfolded, randomly folded chain - denatured The transformation of a native protein into a denatured one, i.e. the protein loses its three-dimensional configuration, is called denaturation(Fig. 3.15). A variety of factors can cause denaturation. In particular, the tight packing of the protein chain is usually disrupted by heating. Thermal denaturation is a general property of proteins. After denaturation, a biologically active protein can spontaneously fold into its original conformation and restore its activity. The process of folding a denatured protein is called renaturation.

Rice. 3.15. Denaturation of a protein molecule:

A- the initial state; b - beginning reversible disruption of the molecular structure; V- irreversible unfolding of the polypeptide chain

With prolonged exposure to a denaturing agent (temperature, chemical substance, environment with different pH), denaturation becomes irreversible (in Fig. 3.15 this process is indicated by an arrow between the states of the protein molecule b And V). Most proteins denature when their solutions are heated above 50-60 °C.

Denatured protein loses its ability to dissolve in water. The most characteristic sign of denaturation is a sharp decrease or complete loss of a protein’s biological activity (catalytic, antigenic or hormonal). The fact that a denatured protein completely loses its biological properties confirms the close relationship between the structure of a protein molecule and the function it performs in the body.

The ability of a protein molecule to spontaneously renature when external aggressive influence is removed suggests that the amino acid sequence itself determines the spatial structure of the protein without the participation of any external regulatory center.

Currently, denaturation and renaturation of globular proteins in vitro are being intensively studied, since these processes are associated with the problem of protein self-organization, i.e., with the question of how a protein chain “finds” its unique structure among a gigantic number of possible alternatives.

Fibrillar proteins form the basis of water-insoluble and durable materials, such as horns, hooves, nails, wool, hair, feathers, skin, tendons, and intercellular substance of bone tissue. Hair is a long, fairly strong fiber, the basis of which is protein - a-keratin. At the heart of tendons is another protein - collagen. Gives elasticity and resilience to the walls of arteries or pulmonary alveoli elastin. A common feature of these proteins is the participation in the formation of their spatial structure of covalent non-peptide bonds.

Keratins hair and wool form intermediate filaments, consisting of long polypeptide chains with large domains formed by a-helices and containing repeating sequences of seven amino acid residues (heptapeptides). Two identically directed chains of keratin form a superhelix, in which the non-polar amino acid residues face inward and are thereby protected from the effects of water. This structure is further stabilized by numerous disulfide bonds formed by cysteine ​​residues of adjacent chains. The supercoiled dimers in turn combine to form tetramers, similar to a four-strand rope.

Collagen formed outside cells from the protein secreted by them - procollagen, which is converted into collagen as a result of the interaction of appropriate enzymes. The procollagen molecule is a triple superhelix formed by three specialized polypeptides twisted together. Further, upon cleavage of terminal polypeptides, tropocollagen, which is packaged into collagen fibers. Each of the three polypeptides in tropocollagen is in the form of a left-handed helix (as opposed to the usual right-handed α-helices in proteins). About a third of the amino acid residues in tropocollagen are represented by proline, and every third residue is glycine.

During collagen formation, many proline and lysine residues are hydroxylated in the presence of ascorbic acid, turning into hydroxyproline and hydroxylysine, respectively:

These residues are included in the protein not during its matrix synthesis, but as a result of chemical post-translational transformation the amino acids it contains. Hydroxylation of proline requires ascorbic acid (vitamin C) as a cofactor (a non-protein component necessary for effective operation), which is needed to maintain the reduced state of the Fe 2+ ion in the active center of the prolyl-hydroxylase enzyme. With a lack of vitamin C, the formation of connective tissues is disrupted, which causes a serious disease - scurvy.

Three helically wound tropocollagen molecules are covalently bonded to each other, forming a strong structure. Such an association is not possible in a conventional protein helix, since bulky side chains prevent it. In collagen, the helices are more elongated (there are 3 residues per turn, instead of 3.6), since every third amino acid residue is glycine, so the helices at these points are as close to each other as possible. Additional stabilization of the structure is carried out by hydrogen bonds of hydroxylated lysine and proline residues.

Tropocollagen molecules contain about 1000 amino acid residues. They assemble into collagen fibrils, joining head to tail. The voids in this structure, if necessary, can serve as a site for the initial deposition of crystals of hydroxyapatite Ca 5 (0H)(P0 4)3, which plays an important role in the mineralization of bones.

Tendon collagen undergoes enzymatic modification - lysine residues are covalently cross-linked at the terminal parts of the tropocollagen chains. Thus, tendons are bundles of parallel oriented fibrils. Unlike tendons in the skin, collagen fibrils form a kind of disordered two-dimensional network.

Elastin its structure differs from collagen and a-keratin. It contains ordinary α-helices forming a cross-linked network, which owes its unusually high elasticity to the unique way in which the lysine side chains are linked:

four closely spaced lysine residues

form the so-called desmosine a structure that combines four sections of peptide chains into one unit (Fig. 3.16).

Rice. 3.16. Chemical structure of desmosine

Globular proteins. Most protein molecules in the body have a globular structure. The peptide bond in globular proteins in their natural state is folded into compact structures - globules, which, to a first rough approximation, can be represented in the form of a ball or a not too elongated ellipsoid, in contrast to fibrillar proteins, where long polypeptide chains are elongated along one axis.

Globules are stable in aqueous systems due to the fact that the polar groups of the main and side chains are concentrated on the surface, being in contact with water, and the non-polar ones face deep into the molecule and are protected from this contact. Ionic bonds are sometimes formed on the surface of the protein globule - salt bridges.

The >N-H and >C=0 groups of the main chain found inside the globule with formed hydrogen bonds form a-helices and (3-layers). The destabilizing factor of spatial packing is the presence in the depths of the globule of some groups that are potentially capable of forming ionic and hydrogen connections, but actually deprived of partners.

Under physiological conditions, the state of a protein with a native three-dimensional structure is thermodynamically stable, i.e., it corresponds to a minimum of free energy. The information necessary for folding a protein into its native conformation is contained in its amino acid sequence. Therefore, in principle, it is theoretically possible to predict the three-dimensional structure of any protein based on its amino acid sequence. However, tertiary structure prediction remains an unsolved problem in molecular biology. The folding of a protein molecule from the unfolded state must be carried out in a single way. If we assume that a protein molecule consists of 50 residues, each of which can take 10 different conformations, then the total number of possible conformations will be 10 50, and if the characteristic time of molecular rearrangements is 10 “13 s, then in order to try all conformations, it will take 10 37 s (~ 10 30 years). Therefore, there is a directed pathway for protein folding.

The stability of a folded protein molecule in an aqueous environment is extremely low. The main driving force for folding is the entropic hydrophobic effect, due to which nonpolar groups tend to leave the aqueous environment and end up inside the globule. There is also the opposite effect, which prevents folding and is due to the fact that for a folded protein molecule the number of allowed conformations of the main and side chains is less than for an unfolded one.

Hemoglobin (Hb)- a protein that carries oxygen from the lungs to the tissues. Hb is localized in red blood cells - erythrocytes.

As already noted (see Fig. 3.14), hemoglobin consists of four polypeptide chains, each of which contains heme (Fig. 3.17). The functional relationship of these chains is such that the addition of O2 to one of the iron atoms increases the oxygen affinity of the other three.

Hemoglobins are a whole class of proteins, the representatives of which differ in one or two amino acid residues or their sequence. An adult has hemoglobin of the HLA type. In addition to HbA, there is fetal hemoglobin HbF, which disappears after birth. The molecular weight of both hemoglobins is approximately the same (64,500); they differ only in the sequence of amino acid residues. Along with the usually existing hemoglobins, abnormal HbS, HbG, HbS, HbH, etc. are found in the human body. The commonality of all hemoglobins is in the way their polypeptide chains are arranged around a large flat ring heme, identical for everyone, in the center of which there is an iron atom (porphyrin ring).

Heme consists of carbon, nitrogen and hydrogen atoms, forming a flat ring called porphyrin (Fig. 3.17). In the center of the ring there is an Fe atom connected to the ring atoms by four coordination bonds (out of six possible). The heme is flanked by two histidine residues (His). The imidazole group of histidine (F-8) is coordinated to the Fe atom through a fifth coordination bond. The sixth bond serves to connect to the O2 molecule.

Rice. 3.17.

Myoglobin- a muscle protein that transports oxygen in muscle cells. It consists of a single polypeptide chain, contains only α-helices connected by loops, and has one heme. The amino acid sequence of myoglobin differs from the sequences of the a-chains of hemoglobin. However, the tertiary structure of the a-chains of hemoglobin and myoglobin is identical. The general method of folding α-helices of globular proteins is called globin type of folding.