Fundamentals of Biochemistry - Filippovich, Y. B. 1999

Proteins
Characteristics of individual protein groups

Catalytically active Proteins. The extensive elucidation of the primary and quaternary structures of catalytically active proteins (Enzymes), coupled with comprehensive data on the Tertiary Structure of several representatives, has led to broader generalizations regarding the Structural Features of proteins in this group and their direct correlation with catalytic function. Without delving into minutiae (see Chapter III), we can outline the key structural characteristics of enzymes as follows.

The α-helical and β-sheet structures found in varying proportions within their molecules lie in close proximity and alternate to pack into functional blocks. Even disordered fragments of the polypeptide chain exhibit partial yet distinct structural Organization, forming structures such as ω-loops and other quasi-structural elements. Charged amino acid residues are typically directed toward the globule surface, whereas only those with specific functional significance associated with other polar residues are oriented inward. Conversely, a limited number of hydrophobic amino acid residues are exposed On the surface; the majority face the interior of the molecule, where they coalesce into one or more hydrophobic cores.

In many enzyme proteins, these cores are similar in structure and, when multiple, serve as centers for The formation of di- or multi-domain protein globules. This architecture is characteristic of many monomeric enzymes (see Fig. 34, illustrating the structures of Ribonuclease and Lysozyme). The Active Site is situated at the interface of two (or more) structured or indistinct Regions of the enzyme molecule, localized within a cleft or depression. The depth, shape, and dimensions of this pocket correspond to the Spatial Structure of the substrate, thereby ensuring the catalytic Specificity of these proteins.

The architecture of the active site itself is so exquisitely organized that it enables the catalytic act to be executed with strict spatial and temporal coordination. Most enzymes feature allosteric sites that mediate contact with Allosteric regulators of their activity. A major proportion of catalytically active proteins possess a quaternary structure, which largely dictates their ability to form Isoenzymes—The Study of which represents an exciting and rapidly expanding field in enzymology.

These fundamental structural features of enzymes demonstrate a profound interrelationship between molecular architecture and the capacity to accelerate specific Chemical Reactions, a hallmark of this extensive group of protein molecules.

Hormone proteins. A defining characteristic of this protein group is their ability to influence fundamental Metabolic Regulation mechanisms, such as Cell membrane permeability and The Biosynthesis of secondary messengers.

The structure and biological activity of several dozen protein Hormones have been thoroughly investigated (see Chapter XII). The molecular weights of the vast majority fall within the range of 20,000 to 30,000 Da. A crucial feature of protein hormones is the presence within their polypeptide chains of relatively small fragments (spanning up to several dozen amino acid residues) that bear the hormonal activity, while the remainder of the chain serves other Functions, notably species-specific ones. Protein hormones contain anchoring domains that secure their binding to the hormone receptor. Their Secondary structure complements or extends that of the receptor, resulting in a complementary, complete complex necessary and sufficient for biological signal generation.

Regulatory proteins. Research into the group of regulatory proteins has intensified dramatically in recent years, as their functional activity is closely tied to the repression and derepression of The Genome and The regulation of vital processes such as growth, development, and morphogenesis in plants and animals.

One of the most extensively studied subgroups of these proteins is the Histones (see p. 81), which are localized in the Chromatin of cell nuclei and associated with DNA. Chromatin-associated histones exhibit limited diversity and are classified into five major types, which various authors have designated by different names or indices over time (Table 9).

Class="center">Table 9 Classification, nomenclature, and PHYSICOCHEMICAL CHARACTERISTICS OF histones

Note. The three-letter nomenclature for histones is based on listing the three predominant Amino Acids in descending order of content, where A stands for Alanine, G for Glycine, E for glutamic acid, K for lysine, L for leucine, P for Proline, R for arginine, and S for Serine. However, despite its descriptive nature, this system has not yet gained widespread use.

The primary structures of histones from various biological sources (chicken erythrocytes, carp Testes, pig, calf, and bovine Thymus, pea seeds, and many others) have been elucidated and found to be remarkably similar within each histone type; moreover, they are highly conserved, with the exception perhaps of histone H1, which varies in both molecular weight and Amino Acid Sequence.

Regarding the secondary and tertiary structures of histones, they are characterized by the presence of short α-helical regions and a dominance of random polypeptide chains that form an extended helix in regions rich in basic amino acids, featuring 2.5 amino acid residues per turn and a pitch of 0.8 nm.

By binding to DNA via ionic bonds and weak interaction forces, histones stabilize its structure. Naturally, the DNA destabilization required for its template activity to manifest is only possible when the bonds between DNA and histones are weakened (due to various factors), which defines the regulatory role of histones in genome function. According to modern data, the first level of Chromatin Structure is organized in the form of nucleosomes (see Ch. VI).

Another subgroup of regulatory proteins, also localized in the Cell Nucleus chromatin, is non-histone proteins. They have been studied to a much lesser extent than histones. These proteins are extremely heterogeneous: when fractionated using Polyacrylamide gel Electrophoresis and isoelectric focusing, about 500 Polypeptides with molecular weights ranging from 5,000 to 200,000 Da are detected. A certain fraction of non-histone proteins actively participates in genome derepression, preventing the formation of supercoiled DNA in those regions where they attached during the S-phase of the Cell Division cycle.

High mobility group non-histone proteins (HMG proteins), which have been studied in considerable detail in recent years, facilitate the binding of histones to DNA, the formation of nucleosomes, and the interaction of hormone-receptor complexes with chromatin.

The list of regulatory proteins, as well as data On the Relationship between their Structure and function, is constantly expanding. Regulatory proteins include: more than a dozen protein factors involved in METABOLISM/36.html">DNA Replication (see Ch. VI); proteins covalently bound to viral and phage DNA and RNA that initiate Nucleic Acid Replication; over 50 nuclear protein factors that enhance or repress Transcription processes (see Ch. VI), with the mechanism by which they recognize specific nucleotide sequences in the DNA molecule via specific oligopeptide fragments within protein transcription factors becoming increasingly clear; over two dozen initiation, elongation, and termination factors that control the assembly stages of polypeptide chains during Protein Biosynthesis (see Ch. VII); heat Shock proteins (and, more broadly, stress proteins) that appear in response to thermal and other stress stimuli, protecting Cells from damage and restoring their metabolism after the removal of physiological stress; G-proteins (some of which have been obtained in homogeneous form and characterized) that regulate the biosynthesis of cyclic adenosine and guanosine monophosphates, which act as secondary messengers in the transmission of hormonal and other signals (see Ch. XIII); oncoproteins, whose antagonism with antioncoproteins leads to malignant cell transformation; and chalones and antichalones, which are related to the Regulation of Cell proliferation.

Undoubtedly, studying the STRUCTURE AND FUNCTIONS of the aforementioned proteins opens up Prospects for understanding the fundamental principles of life processes, including at the genome level; Current Concepts of the types of interactions between regulatory proteins and DNA are illustrated in Fig. 41.

Protective proteins. Antibodies belong to the group of protective proteins; these are proteinaceous substances produced by the animal Organism in response to the Introduction of Antigens. By interacting with the latter, they inactivate them, thereby protecting the organism from the effects of foreign compounds, Viruses, Bacteria, cells, and Tissues. To designate proteins synthesized in the body in response to antigenic challenge, the term IMMUNOGLOBULINS (abbreviated as Ig) was proposed. Since they were first discovered in the slowly migrating γ-globulin fraction of Blood Serum proteins during electrophoresis, they are also referred to as γ-immunoglobulins.

Fig. 41. Modes of binding of regulatory proteins to DNA

On the left side of the figure, crossed α-helices of a regulatory protein interact with symmetrically arranged binding sites in the DNA double helix located within the major groove of DNA. The recognition α-Helix is shown as a dark cylinder, and another α-helix located above it (white cylinder) assists in recognizing the binding site. In the middle portion of the figure is a ββ'α-supersecondary structure with a Zn atom at the center (coordinated to two Cysteine residues (C) of the β-sheet and two Histidine residues (H) of the α-helix), which provides an electrostatic type of binding to DNA through a dipole within the ββ'α-structure (polar regions are hatched). On the right side of the figure is a regulatory protein dimer held together by a hydrophobic zipper of leucine-rich α-helices; the dashed line indicates the axis of rotational Symmetry; hatched rectangles represent highly basic fragments that directly interact with DNA, and arrows point to paired half-centers for recognizing the binding site in DNA.

According to the modern classification, there are 5 classes of immunoglobulins (IgG, IgM, IgA, IgD, and IgE), whose molecular structural elements are represented by light and heavy polypeptide chains (Fig. 42). Their molecular weights range from 150,000 to 950,000 Da. The heavy chains of various immunoglobulins are designated by lowercase letters of the Greek alphabet corresponding to the uppercase letters of the Latin alphabet used to indicate the immunoglobulin class, i.e., for IgG it is γ (gamma); for IgM, μ (mu); for IgA, α (alpha); for IgD, δ (delta); and for IgE, ε (epsilon). The heavy polypeptide chains (H-chains) differ among various immunoglobulin classes. Conversely, the light polypeptide chains (L-chains) exist in only 2 types across different immunoglobulins: κ (kappa) and λ (lambda). In turn, the existence of subclasses has been noted for certain immunoglobulins, such as IgG₁, IgG₂, IgG₃, and IgG₄, which differ slightly in the Primary Structure of their polypeptide chains. The bulk of human serum immunoglobulins consists of IgG (75–85% of their total amount); IgA is present at 7–15%, IgM at 5–10%, IgD at 0.3%, and IgE at 0.003% (also of the total amount). Furthermore, IgA is localized in secretions (tears, saliva, Bile, intestinal juice, etc.) and Lymph.

The primary STRUCTURE OF THE heavy and light chains of many immunoglobulins has been elucidated: the heavy chains contain from 439 to 450 amino acid residues (γ-chains) and from 568 to 576 residues (μ-chains), while the light chains contain from 208 to 220. A striking feature is that both light and heavy immunoglobulin chains reveal variable domains located predominantly in the first half of the chain, i.e., at the amino-terminal end. In contrast, the primary structures of the light and heavy chains in various immunoglobulins are similar in their second half, i.e., toward the C-terminal amino acid. The variable region of the molecule is responsible for the interaction of immunoglobulins with A wide variety of antigens, whereas the region with a relatively constant primary structure performs functions common to all immunoglobulins (Complement binding, membrane fixation).

Fig. 42. Structure of human immunoglobulin G1

Two light and two heavy polypeptide chains are linked in pairs by disulfide (—S—S—) bonds; each chain contains internal disulfide bridges that delineate various domains; C_H1, C_H2, C_H3 are the constant domains of the heavy chain

The higher-level structural parameters of various immunoglobulins are even more uniform and are referred to as the immunoglobulin fold, characterized by a standard spatial arrangement of domains relative to one another and GENERAL PATTERNS OF their three-dimensional orientation.

CARBOHYDRATES, which make up 2 to 12% of their composition, play a definite role in the functioning of immunoglobulins. They are attached to the light and heavy chains of immunoglobulins primarily via asparagine residues and, in some cases, Threonine residues, and are represented by Oligosaccharides containing N-acetylglucosamine, mannose, galactose, fucose, and sialic acid in a ratio that is most often close to 4:3:2:1:1.

Thus, The structure of immunoglobulins exhibits a remarkably subtle interplay between structure and function, vividly demonstrating the specific Molecular organization of proteins endowed with a distinct—in this case, protective—biological activity.

In addition to immunoglobulins, protective functions are performed by Blood Coagulation SYSTEM proteins, interferons, interleukins, antifreeze proteins, haptoglobins, Histocompatibility Antigens, lysozymes, plant antiviral proteins, and insect antibacterial proteins.

Toxic proteins. The group of toxic proteins has been studied quite intensively in recent years due to its great practical significance.

From the perspective of primary structure, the most complete information has been obtained on snake toxic proteins: their Amino acid sequences have been deciphered for several dozen toxins derived from the venoms of forest, African, Asian, Egyptian, king, Mozambican, Indian, and other cobra species, African green and black tree snakes, sea snakes, and others.

It is extremely fascinating that snake venom toxins, with molecular weights ranging from 6,700 to 7,000 Da, are composed in most cases of 60 amino acid residues; scorpion, bee, and wasp toxic polypeptides are of approximately the same size; close to them (45 amino acid residues) are toxins from wheat flour (purothionin A, lethal to brewer's Yeasts), sea anemones, and European mistletoe (viscotoxins). The overwhelming majority of these are neurotoxins, as they interact with cholinergic proteins and block the transmission of nerve impulses. Their neurotoxic effect depends on the tertiary structure, which is largely determined by numerous (4–5) disulfide bridges (see the structure of erabutoxin in Fig. 40).

High-molecular-weight protein toxins of microorganisms and plants have been studied with almost equal detail. The structure and MECHANISM OF ACTION of several dozen of them have been elucidated. In some cases, they are multimers (diphtheria and cholera toxins, Shigella toxin, etc.) constructed from a single type A subunit (20.0, 28.0, and 32.0 kDa, respectively) and five type B subunits (25.0, 12.0, and 7.7 kDa, respectively). By contacting The Cell surface via type B subunits, they translocate the type A subunit into the cell, where it blocks protein biosynthesis on Ribosomes. In others, they are two-component systems (plant toxins—ricin, abrin, modeccin, lectin, etc.), wherein subunit B binds to cell receptors and ensures the translocation of subunit A into the cell, leading to the inactivation of the 60S ribosomal subunit and the cessation of Protein Synthesis. In still others, they are single-chain proteins (Staphylococcus enterotoxin, Escherichia coli hemolysin, streptolysin, etc.), and their large polypeptide chains (from 34 to 110 kDa) insert into The cell membrane, forming pores that lead to cell lysis. Here, as in the case of neurotoxins, a close relationship between the structure and function of toxic proteins is clearly traceable.

Transport proteins. A classic representative of transport proteins is serum albumin. It has been isolated in a highly purified state, and its production has been established on a preparative scale. The primary function of this protein is The transport of various substances, especially Fatty acids. In addition to Higher Fatty Acids, for which serum albumin has a very high affinity, it transports a variety of anions and cations. Serum albumin binds up to 50% of the calcium present in the blood, acts as a carrier for copper ions from the intestine to the Liver, and serves as a carrier for Steroid Hormones. The Molecular Weight of human serum albumin is 65,000, and its isoelectric point (pI) is 4.7 (at an Ionic strength of 0.15). It is capable of forming dimers with a sedimentation coefficient of 6.7S. The primary structure of human serum albumin, consisting of 585 amino acid residues, has been elucidated.

Among other human serum proteins possessing transport functions are ceruloplasmin ($M = 160,000$, $pI = 4.4$), which transports copper ions from the liver to cell Organelles; transferrin ($M = 90,000$, $pI = 5.9$), which transports ferric ions; $\beta$-lipoprotein ($M = 3,200,000$, $pI = 5.4$), which transports Lipids, Fat-soluble Vitamins, and hormones—a function also characteristic of other serum Lipoproteins. Very low-density lipoproteins in humans transport 25–50 g of endogenous triglycerides daily, while other types transport Cholesterol, $\beta$-carotene, Phospholipids, Hydrocarbons, and acyclic alcohols. Well-known Oxygen-transporting proteins include vertebrate and certain lower animal Hemoglobins, molluscan, crustacean, arachnid, and horseshoe crab hemocyanins, annelid hemerythrins (brown respiratory proteins), polychaete chlorocruorins (green respiratory proteins), and vanadium-containing hemovanadins of marine animals ( tunicates ).

Transport proteins are characteristic not only of biological fluids. In recent years, researchers' attention has been particularly drawn to proteins embedded in the outer and inner membranes of cells, which mediate the transport of various low- and high-molecular-weight substances across them. These proteins are termed porins because they form pores in membranes through which transport occurs. Some of these proteins (porin I from the outer membrane of Escherichia coli—molecular weight 37,205 Da, 340 amino acid residues; porin from rat liver Mitochondria—a dimer of two identical polypeptides, etc.) have been isolated and characterized. This category also includes translocases, The Mechanism of substance transport across membranes by which is illustrated in Fig. 43.

Fig. 43. Transmembrane Transport of substances mediated by proteins:

A — rotating carrier protein; B — mobile carrier protein; C — pore formed by carrier proteins

Structural proteins. Numerous and diverse proteins perform structural functions in biological entities.

This role is primarily fulfilled by proteins that constitute various Biological Membranes, excluding, of course, those endowed with other functional activities (membrane-bound enzymes, pore proteins, carrier proteins, receptor proteins, etc.).

Data on the molecular weights of membrane structural proteins are contradictory. For structural proteins of bovine Heart and liver mitochondria, they range from 20,000 to 60,000, whereas in bacteria, they range from 10,000 to 160,000 Da. Membrane structural proteins exhibit a pronounced tendency toward aggregation. At pH 12, they exist as monomers, but upon lowering the pH, they oligomerize to form fibrillar structures and microcrystals. Furthermore, they are capable of combining in stoichiometric ratios with other proteins (e.g., Myoglobin) and especially with enzymes characterized by membrane localization (Cytochromes $c_1$ and $b$, cytochrome oxidase, malate dehydrogenase, etc.), with the catalytic activity of the latter changing markedly As a result. Therefore, it is believed that The Role of membrane structural proteins is not limited merely to anchoring enzymes within the membrane.

The properties of membrane structural proteins are largely predetermined by their Amino Acid Composition. They contain a high proportion of amino acids with hydrophobic radicals (glycine and alanine—10–15%; valine, leucine, and isoleucine—on average 5–6% each, and in some cases up to 9–13%), while the content of basic and acidic amino acids is relatively low. Most intriguingly, hydrophobic amino acids form local zones (segments) within the polypeptide chain of membrane structural proteins, comprising 20 or more exclusively hydrophobic amino acid residues and accounting overall for up to 20% of the entire polypeptide chain length. This facilitates the formation of hydrophobic centers within the molecules of membrane structural proteins, including centers localized on the globule surface. This circumstance largely explains the high aggregation capacity of these proteins, as well as the fact that subunits in oligomers are held together by weak interaction forces.

Another significant consequence follows from The amino acid composition of membrane structural proteins. The content of amino acids that hinder $\alpha$-helix formation is such that the proportion of $\alpha$-helical structure can average 40% of the polypeptide chain. Indeed, experimental data obtained by infrared spectrophotometry, optical rotatory dispersion, and circular dichroism indicate that a significant portion of the polypeptide chain of membrane structural proteins exists in an $\alpha$-helical conformation (from 30 to 50%).

Finally, another specific property of membrane structural proteins is that all of them, regardless of their source, readily bind phospholipids at neutral pH values. Since phospholipids retain their charge in the process, the binding of membrane structural proteins and phospholipids proceeds via weak interaction forces, i.e., through the hydrophobic centers of the proteins and the hydrocarbon radicals of the phospholipids.

In addition to Membrane Proteins, structural functions are performed by Extracellular matrix proteins (Collagen, reticulin), crystallins, as well as nuclear matrix and cytoskeletal proteins. The number of the latter, partially or fully characterized, has now reached several dozen, representing one of the most pressing challenges in modern Protein Chemistry.

Contractile proteins. Contractile proteins are localized in both animal Muscle cells and non-muscle cells of primitive and highly organized living organisms. These include myxomyosin (a filamentous protein with a molecular diameter of 7.0 nm, isolated from the plasmodium of the slime mold Physarum); microtubule proteins (subunit diameter in the tubule 4.5–7.0 nm), which ensure protoplasmic streaming in PLANT AND ANIMAL cells; Myosin- and Actomyosin-like Proteins of the fibrillar apparatus of Amoeba, responsible for the cytoplasmic streaming of its protoplasm; proteins of tubular fibrils involved in chromosome movement during cell division; proteins of the central and peripheral fibrils of protozoan flagella and cilia, as well as sperm flagella; and Actin and myosin of muscle fibers.

In addition to their contractile properties, the vast majority of the contractile proteins listed above exhibit adenosine triphosphatase activity; that is, they combine two distinct functions—The ability to perform mechanical work and to accelerate chemical reactions. This property of contractile proteins was discovered in 1939 by V. A. Engelhardt and M. N. Lyubimova, who published their experimental results in the October issue of Nature (Vol. 144, p. 688) in an article entitled "Myosin and Adenosine Triphosphatase." Thus, these proteins are characterized by mechanochemical properties. A common feature inherent to contractile proteins is that their function depends on the action of A number of auxiliary proteins—activators and regulators of their activity—as well as on the presence of low-molecular-weight compounds (Mg²⁺, Ca²⁺, ADP). For instance, The activity of the muscle actomyosin complex is regulated by Tropomyosin and troponin.

Specific data on contractile proteins isolated from various sources vary in completeness and reliability, and in some cases are contradictory. Muscle myosin and actin have been studied the most thoroughly. Myosin is a fibrous protein with a molecular weight of 500,000 Da, whereas actin is a globular protein with a molecular weight ranging from 46,000 to 58,000 Da (Fig. 44). The primary structure of a myosin chain fragment spanning up to 200 amino acid residues—which accounts for approximately one-tenth of its polypeptide chain—has been elucidated. Scientists have also successfully deciphered the primary structure of actin from rabbit muscle, a protein consisting of 374 amino acid residues. Actin exhibits a strong propensity for aggregation, proceeding with the formation of supramolecular structures in the form of supercoiled long double filaments.

Information regarding other contractile proteins is less comprehensive. Myxomyosin has a molecular weight of approximately 6,000,000 Da and Molecular dimensions of 7 × 400–500 nm. The contractile protein isolated from protozoan cilia closely resembles muscle myosin in molecular weight (400,000), amino acid composition, and properties. However, the contractile protein from mitotic spindle fibrils is globular (globule diameter ranging from 15 to 20 nm, M = 880,000) and is characterized by a subunit structure. Microtubule tubulin is represented by a dimer with a molecular weight of 110,000 Da.

Elucidating the structure and, in particular, the mechanism of action of contractile proteins is of immense interest and is still very far from complete.

Receptor proteins. The classification of receptor proteins into a distinct group is associated with intensive research into the Mechanisms of signal Transduction in biological systems.

The targets of agents carrying signaling functions are receptor proteins localized in the cellular membrane apparatus. One example is the receptor for acetylcholine, a neurotransmitter involved in Nerve Impulse transmission (see Ch. III). It is represented by an oligomeric protein (M = 285,000) composed of five subunits (α₂βγδ) that form an ion channel (Fig. 45). In the absence of acetylcholine, this channel is closed, but upon reception of secreted acetylcholine, it opens briefly (until the neurotransmitter is degraded by acetylcholinesterase) to allow the passage of Na⁺, which is accompanied by A change in the degree of polarization of the Cell Membrane and signal transmission across the nerve cell synapse.

Fig. 44. Diagram of the structure of muscle contractile proteins:

I — structure of the myosin molecule, composed of two polypeptide chains comprising about 1,800 amino acid residues each. The major part of the molecule is represented by a supercoil (horizontal part of the figure) formed by two almost completely helical polypeptide chains; the smaller part consists of two polypeptide chain fragments in a globular state, where the content of α-helices reaches 30% (the HEAD responsible for actin binding and ATPase activity). The tail region (light meromyosin) is cleaved from the head region (heavy meromyosin) as a result of proteolytic Digestion with Trypsin. The globular part (head) is cleaved off by Papain proteolysis; II — supercoil composed of actin globules. Each sphere in the figure corresponds to an actin molecule (M = 46,000); III — attachment point of the myosin molecule heads (indicated by arrows) to the actin supercoil During Muscle contraction

Recent studies have shown that the reception of various types of environmental energy by Sense Organs shares a uniform mechanism comprising two stages: 1) perception of the stimulus energy by receptor proteins; 2) Conversion of the stimulus energy by specialized protein molecules into specific information and its transmission to the Central Nervous system.

Data on receptor proteins and the mechanism of their interaction with environmental signals are quite sparse. A representative photoreceptor protein is opsin, which exists as a complex with retinal (rhodopsin) and undergoes a conformational change associated with The conversion of a light signal into nerve impulses during the visual process (see Ch. IV, Fig. 60). Among taste receptor proteins, the sweet-sensing protein has been studied (M = 150,000). Its amino acid composition is characterized by a high content of dicarboxylic Amino Acids and their amides, lysine, leucine, valine, and proline. It is capable of binding mono- and Disaccharides. The olfactory protein has been isolated from the sex sensilla of male oak silkmoths; it interacts with the sex pheromone of females of this insect species. Cholinoreceptive proteins, which have recently been shown to be responsible for cell membrane permeability, are considered to play a major role in the perception of sound vibrations and their conversion into nerve impulses.

Fig. 45. Structure of the Acetylcholine Receptor

In the upper left corner is the oligomeric form of the receptor, showing the spatial structure of the α-subunit (M = 40,000) that makes up the pentamer; the circle in the center of the pentamer is the ion channel with a diameter of 0.65 nm. In the lower part of the figure is the unfolded structure of the receptor α-subunit embedded in The Plasma Membrane of the cell; the helical regions of the α-subunit polypeptide chain are enriched with hydrophobic amino acid radicals that interact with higher fatty acid residues of the phospholipid membrane; starting from the N-terminus, The polypeptide chains of the subunits are glycosylated, with the carbohydrate component accounting for approximately 20% of the receptor mass; C192 and C193 are cysteine residues involved in acetylcholine reception

Great prospects are opening up in the study of insect receptor proteins, especially those involved in the reception of attractants and repellents.

Enzyme inhibitor proteins. Proteinaceous substances constitute the largest group of Enzyme Inhibitors, with proteins that inhibit protease activity being the most thoroughly studied. Protein inhibitors form stable complexes with Proteolytic Enzymes under physiological conditions, within which the enzyme completely or partially loses its activity. Since the dissociation constants of these complexes lie within the range of 10^-12–10^-9 mol, they are indeed characterized by high stability, and the inhibitors comprising them exhibit high potency.

Several dozen protein inhibitors that suppress the activity of trypsin, Chymotrypsin, carboxypeptidase, kallikrein, Elastase, plasmin, and other proteolytic enzymes have been isolated and studied. Many of these have been obtained in a homogeneous crystalline state. The molecular weights of proteinaceous inhibitors range from several thousand to several hundred thousand, but they are predominantly represented by proteins with molecular weights of about 6,000 Da. Many enzyme inhibitor proteins are Glycoproteins. The primary structure of several dozen inhibitors has been deciphered; among them are trypsin inhibitors I and II from porcine and bovine Pancreas, soybeans, peanuts, and Kidney beans; proteinase inhibitors from viper venom, lima beans, and pineapple; the chymotrypsin inhibitor from potatoes; the kallikrein inactivator (Trasylol) from bovine Lungs; the subtilisin inhibitor from Streptomyces, etc.

Viral coat proteins. Various proteins have been isolated from numerous viruses and studied. Their molecular weights range from several thousand to several tens of thousands of daltons. Alongside their primary function (protection of nucleic acid), certain viral coat Proteins are essential for the maturation of Viral Particles, exhibit enzymatic activity (such as neuraminidase, lysozyme, and Reverse Transcriptase found in a number of viruses), and perform other functions.

The primary structure of protein subunits from many viruses has been elucidated. These include the subunits of three strains of tobacco mosaic virus (159 amino acid residues), Bacteriophages fr and f2 subunits (129 residues), bacteriophage Q_β (131 residues), bacteriophage ZI (50 residues), turnip yellow mosaic virus subunits (190 residues) and silkworm nuclear polyhedrosis virus subunits (244 residues), bacteriophage fd subunits (50 residues), as well as a number of Influenza virus proteins (hemagglutinin—566 and PV2—759 amino acid residues).

A striking feature of viral proteins is their ability to aggregate, as a result of which, even in the absence of viral Nucleic Acids, they are capable of self-assembling into corresponding morphological structures characteristic of a given virus (viral and phage ghosts). Furthermore, their structure is such that terminal Amino acids are generally masked deep within the molecule and are difficult to access for determination.

Proteins with other functions. It is certain that new groups with clearly defined functional activities and associated specificities of Structure and properties will continue to be segregated from the extremely numerous specific Representatives of the protein class. For instance, groups such as hemoglobins, Fibrous proteins, and ribosomal proteins are already being delineated. This merely reinforces the aforementioned view that Protein Classification is currently undergoing a period of establishment.