BIOCHEMISTRY - Textbook - Ostapchenko L. I. - 2012

Chapter 5. STRUCTURE, PROPERTIES, AND FUNCTIONS OF PROTEINS

5.6. Protein diversity and classification

5.6.1. Classification of proteins based on molecular shape

One of the oldest classifications divides Proteins into two groups—globular and fibrillar—based on their molecular shape. Globular proteins are those in which The ratio of the longitudinal axis to the transverse axis does not exceed 1:10, and most commonly ranges from 1:3 to 1:4, meaning the protein molecule has an ellipsoid shape. The majority of individual human proteins are globular. They feature a compact Structure, and many of them are readily Water-soluble due to the burying of hydrophobic radicals inside the molecule. Clear Examples of the Structure and function of globular proteins (Hemoglobin and Myoglobin) were discussed above.

Fibrillar Proteins possess an elongated, thread-like structure in which the ratio of the longitudinal and transverse axes is greater than 1:10. This group includes collagens, Elastin, and keratin, which perform structural Functions in the Organism, as well as Myosin, which is involved in Muscle contraction, and fibrin, a protein of the Blood clotting system. Using collagens and elastin as examples, we will examine the Structural Features of these proteins and how their structure relates to their functions.

Collagens are a family of fibrillar proteins secreted by Connective Tissue Cells. They are the most abundant proteins not only in the Extracellular matrix, but in the entire body, accounting for 1/4 of all human body proteins. In the extracellular matrix, Collagen molecules form polymers called collagen fibrils. Collagen fibrils are extremely strong and virtually inextensible. They can withstand loads up to 10,000 times their own weight. In terms of tensile strength, collagen fibrils surpass steel wire of the same diameter. This is precisely why A large number of collagen fibers, composed of collagen fibrils, are found in Skin, tendons, Cartilage, and bones.

The unusual mechanical properties of collagens are related to their primary and spatial structures. Collagen molecules consist of three polypeptide chains known as α-chains. Over 20 α-chains have been identified, most of which consist of 1,000 amino acid residues, though the chains differ slightly in their Amino Acid Sequence. Collagens may contain three identical or different chains.

The Introduction/19.html">Primary Structure of collagen α-chains is distinctive because every third amino acid in the polypeptide chain is Glycine, about 1/4 of The amino acid residues are Proline or 4-hydroxyproline, and about 11% are Alanine. Amino Acids such as Cysteine and Tryptophan are absent in collagen, while Histidine, Methionine, and Tyrosine are present only in very small amounts. The primary STRUCTURE OF THE collagen α-chain also contains an Unusual amino acid: hydroxylysine. The collagen polypeptide chain can be represented as a sequence of Gly-X-Y triplets, where X and Y can be any amino acids, though proline is most frequently found in position X, and hydroxyproline or hydroxylysine in position Y. Each of these amino acids is crucial for The formation of collagen fibrils.

Due to its structure, proline introduces bends into the polypeptide chain, stabilizing a left-handed helical conformation. There are 3 amino acid residues per turn of the helix, rather than 3.6 as is typical for the Secondary structure of globular proteins. The helix of the collagen peptide chain is stabilized not by Hydrogen Bonds (since proline does not form them), but by steric repulsion forces between the pyrrolidine rings in the proline residues. As a result, the distance between amino acid residues along the axis of the helix increases, making it more extended compared to the tightly wound α-Helix of globular proteins.

The helical polypeptide chains intertwine with one another to form a three-stranded right-handed superhelical molecule frequently called tropocollagen (Fig. 5.40). The chains are held together by hydrogen bonds formed between the amino and carboxyl groups of the peptide backbone of different polypeptide chains comprising the triple-helical molecule. "Rigid" amino acids—proline and hydroxyproline—restrict the Rotation of the polypeptide backbone, thereby increasing the Stability of the triple helix. Glycine, which has a hydrogen atom instead of a side chain, is always located at the points where the chains intersect; the lack of a side chain allows the chains to pack closely together.

Class="center">

Fig. 5.40. Structure of a tropocollagen molecule (fragment)

As a result of this twisting of the peptide backbones of The polypeptide chains and the presence of an elongated structure, the other two radicals from the Gly-X-Y amino acid triad end up on the outer surface of the tropocollagen molecule. Certain complementary regions of tropocollagen molecules can associate with one another to form collagen fibrils, and these regions are arranged such that one tropocollagen strand is staggered relative to another by approximately 1/4 (Fig. 5.41). Ionic, hydrogen, and Hydrophobic bonds form between the amino acid radicals.

Fig. 5.41. Structure of a collagen fibril (fragment)

Modified amino acids—hydroxyproline and hydroxylysine—play an essential role in the formation of collagen fibrils. The hydroxyl groups of hydroxyproline in adjacent tropocollagen chains form hydrogen bonds that reinforce The structure of collagen fibrils. Lysine and hydroxylysine radicals are necessary for the formation of strong cross-links between tropocollagen molecules, which further strengthen the collagen fibril structure. Furthermore, carbohydrate residues can attach to the hydroxyl group of hydroxylysine (collagen glycosylation), the function of which remains unclear.

Thus, the amino acid sequence of collagen polypeptide chains allows for the formation of a uniquely strong structure with exceptional mechanical properties. Alterations in the primary structure of collagen can lead to The Development of Hereditary diseases.

Unlike collagen, which forms rigid fibrils capable of withstanding heavy loads, elastin (also an extracellular matrix protein) possesses rubber-like properties. Elastin fibers found in lung Tissues, blood vessel walls, and elastic ligaments can stretch several times their normal length, but return to their coiled conformation once the load is removed.

Elastin contains about 800 amino acid residues, predominantly featuring amino acids with nonpolar side chains, such as glycine, valine, and alanine. Elastin contains a fair amount of proline and lysine, but very little hydroxyproline; hydroxylysine is entirely absent.

The presence of a large number of hydrophobic radicals prevents the formation of a stable globule; consequently, elastin polypeptide chains do not form regular secondary and tertiary structures, but instead adopt various Conformations in the extracellular matrix with approximately equal Free energy (Fig. 5.42). This is a prime example of a primary structure where the absence of a single stable, ordered conformation gives rise to the protein's required properties.

Fig. 5.42. Random conformations of the elastin molecule