BIOCHEMISTRY - Textbook - Ostapchenko L. I. - 2012

Chapter 5. STRUCTURE, PROPERTIES, AND FUNCTIONS OF PROTEINS

5.2. Protein Structure

5.2.2. Secondary Protein Structure

Secondary Cell/13.html">Protein Structure is the spatial arrangement formed through interactions between functional groups that make up the peptide backbone. In this process, peptide chains can adopt two regular structural types: the α-Helix and the β-structure.

α-Helix. In this type of structure, the peptide backbone coils into a helix due to The formation of Hydrogen Bonds between the oxygen atoms of carbonyl groups and the nitrogen atoms of amino groups within peptide groups separated by 4 amino acid residues. The Hydrogen bonds are oriented along the helical axis (Fig. 5.5). One turn of the α-helix contains 3.6 amino acid residues.

Fig. 5.5. α-Helix.

The Spatial Structure of the α-helical region of the polypeptide chain and the formation of hydrogen bonds involved in shaping the α-helix are depicted.

Virtually all oxygen and hydrogen atoms of the peptide groups participate in hydrogen bonding. As a result, the α-helix is "stabilized" by A large number of hydrogen bonds. Although such bonds are classified as weak, their sheer number ensures the maximum possible Stability of the α-helix. Since all hydrophilic groups of the peptide backbone typically take part in Hydrogen bond formation, the hydrophilicity (i.e., The ability to form hydrogen bonds with Water) of α-helices decreases, while their Hydrophobicity increases.

The α-helical structure is the most stable conformation of the peptide backbone, corresponding to a minimum of Free energy. The formation of α-helices shortens the polypeptide chain, but if conditions are created to break the hydrogen bonds, the chain will elongate again.

Amino acid radicals are located on the outer surface of the α-helix, projecting outward in various directions from the peptide backbone. They do not participate in the hydrogen bonds characteristic of the Secondary structure, but some of them can disrupt α-helix formation. These include:

Proline, whose nitrogen atom is part of a rigid ring that prevents rotation around the -N-CH- bond. Furthermore, proline's nitrogen atom, which forms a peptide bond with another amino acid, lacks a hydrogen atom. Consequently, proline is unable to form a hydrogen bond at this specific site of the peptide backbone, disrupting the α-helix structure. This typically results in a loop or bend at the peptide bond;

regions where several identically charged radicals are sequentially positioned, generating electrostatic repulsive forces between them;

regions with closely positioned bulky radicals that mechanically hinder α-helix formation, such as Methionine and Tryptophan.

The β-structure is formed by numerous hydrogen bonds between peptide group atoms of linear segments within a single folded polypeptide chain or between different polypeptide chains. The β-structure forms a pleated sheet resembling accordion folds (Fig. 5.6).

When hydrogen bonds form between peptide backbone atoms of different polypeptide chains, they are referred to as interchain bonds. Hydrogen bonds occurring between linear segments within a single polypeptide chain are called intrachain bonds. In β-structures, hydrogen bonds are oriented perpendicularly to the polypeptide chain.

If the bonded polypeptide chains run in opposite directions, an antiparallel β-structure is formed; if the N- and C-termini of The polypeptide chains run in the same direction, a parallel β-sheet structure is produced (Fig. 5.7).

Fig. 5.6. Secondary protein structure as a β-pleated sheet

Fig. 5.7. Parallel and antiparallel β-pleated sheets:

A - antiparallel β-structure; B - parallel β-pleated structures. β-structures are indicated by broad arrows

Unlike α-helices, the breaking of hydrogen bonds that form β-structures does not cause specific Regions of the polypeptide chains to lengthen. Both α-helices and β-structures are found in globular and Fibrous Proteins.

Proteins also contain regions with irregular secondary structure, commonly referred to as random coils. These are loop-like and ring-like structures with lower packing regularity than the aforementioned α-helices and β-structures. Nevertheless, they do not vary wildly among different protein molecules either. In each individual protein, they maintain a fixed conformation determined by the Amino Acid Composition of the specific chain segment and its surrounding regions.

The term "random coil" is also frequently used to describe a denatured protein that has lost its ordered structure following the rupture of weak intramolecular bonds.

The proportion of these secondary structural types varies among different proteins. Based on the presence of α-helices and β-structures, Globular proteins can be divided into four categories:

1) the first category includes proteins whose structure contains exclusively α-getCelled helices. These include proteins such as Myoglobin and Hemoglobin (Fig. 5.8);

Fig. 5.8. Eight α-helices in The structure of myoglobin (A) and the β-chain of hemoglobin (B)

2) the second category comprises proteins with α-helices and β-structures, which sometimes form recurring combinations found in various individual proteins (Fig. 5.9).

Characteristic combinations of α-helices and β-structures identified in many Enzymes can be illustrated by the domain structure of Lactate dehydrogenase (LDH) and phosphoglycerate kinase (PGK). A domain is a region of a polypeptide chain that, independently of other regions in the same chain, folds into a structure that closely resembles a globular protein.

Fig. 5.9. α-Helices and β-structures in the domain of lactate dehydrogenase (A) and phosphoglycerate kinase (B)

In one of the lactate dehydrogenase domains, β-structures of the polypeptide chain forming a twisted sheet are located in the center, and each β-structure is connected to an α-helical region situated On the surface of the molecule. A similar domain is also found in the phosphoglycerate kinase molecule (Fig. 5.9).

3) the third category includes proteins that possess exclusively β-structures. Such structures are found in IMMUNOGLOBULINS and the enzyme superoxide dismutase (Fig. 5.10).

Fig. 5.10. β-Pleated secondary structure in the constant domain of an immunoglobulin (A) and in the enzyme superoxide dismutase (B)

4) the fourth category includes proteins that contain only a minimal amount of regular secondary structures.