BIOCHEMISTRY - Textbook - Ostapchenko L. I. - 2012

Chapter 5. STRUCTURE, PROPERTIES, AND FUNCTIONS OF PROTEINS

5.2. Protein Structure

5.2.4. Supersecondary Protein Structure

The Spatial Structure of each protein is unique and determined by its Primary Structure. However, comparing the Conformations of Proteins with different structures and Functions reveals the presence of similar combinations of Secondary structure elements among them. This specific pattern of secondary structure formation is referred to as the supersecondary structure of proteins. This structure is formed through inter-radical (side-chain) interactions.

Certain characteristic combinations of α-helices and β-structures are often designated as "Structural motifs." They have specific names such as "α-Helix - turn - α-helix," "β-barrel structure," "leucine zipper," "zinc finger," etc. The specific spatial arrangement of α-helices and β-structures is formed through inter-radical interactions.

The β-barrel type of supersecondary structure indeed resembles a barrel, in which each β-structure (indicated by an arrow in Fig. 5.16) is located internally and connected to an α-helical region of the polypeptide chain situated On the surface of the molecule.

The supersecondary structure in the form of a β-barrel is found in certain Enzymes, such as Triosephosphate isomerase and one of the domains of Pyruvate kinase (Fig. 5.16).

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Fig. 5.16. Supersecondary structures in the form of a β-barrel:

A - triosephosphate isomerase, B - pyruvate kinase domain

The α-helix - turn - α-helix structural motif is found in many DNA-binding proteins. The double-helical structure of DNA has two grooves: a major groove and a minor groove. The major groove is well-suited for binding proteins with small Structural domains.

This structural motif includes two α-helices (one shorter, one longer) connected by a turn of the polypeptide chain. The shorter α-helix lies transversely across the groove, while the longer one resides in the major groove, forming non-covalent specific bonds between amino acid side chains and DNA NUCLEOTIDES (Fig. 5.17).

The "zinc finger" supersecondary structure is also frequently found in DNA-binding proteins. A "zinc finger" is a protein fragment containing about 20 amino acid residues, in which a zinc atom is coordinated with the side chains of four Amino Acids: typically two Cysteine residues and two Histidine residues (Fig. 5.18).

Two closely spaced cysteine residues are separated from two other histidine (or cysteine) residues by an Amino Acid Sequence consisting of approximately 12 amino acid residues. This protein region forms an α-helix that can specifically bind to regulatory regions in the major groove of DNA. The Specificity of the interaction between a DNA-binding protein and a specific DNA sequence depends on The amino acid residues located within the "zinc finger" region.

Fig. 5.17. Binding of the α-helix - turn - α-helix supersecondary structure of a DNA-binding protein in the major groove of DNA

Fig. 5.18. Fragment of a DNA-binding protein in the form of a "zinc finger"

Some DNA-binding proteins are oligomeric, meaning they consist of multiple polypeptide chains. Additionally, there are proteins that function in complexes with other proteins. The assembly of protomers or individual proteins into complexes is sometimes achieved via structural motifs known as "leucine zippers."

On The surface of each of the two interacting peptide chains or proteins, there is an α-helical region containing at least 4 leucine residues. The leucine residues are spaced every 6 amino acids apart. Since each turn of the α-helix contains 3.6 amino acid residues, the leucine side chains appear on the surface of every second turn.

The leucine residues of an α-helix from one protein can interact with the leucine residues of a second protein via hydrophobic interactions, holding them together (Fig. 5.19).

Fig. 5.19. "Leucine zipper" between the α-helical regions of two proteins

An example of protein association mediated by a "leucine zipper" is found in Histones—Nuclear Proteins rich in positively charged amino acids, namely Arginine and Lysine. Histone molecules assemble into complexes consisting of eight monomeric proteins held together by "leucine zippers," despite all the monomers carrying a strong positive charge.

Protein domain structure. If a protein's polypeptide chain contains more than 200 amino acids, its spatial structure is typically formed by two or more domains. A domain is a region of a polypeptide chain that, during The formation of the spatial structure, adopts the conformation of a globular protein independently of other Regions of the same chain. For instance, the immunoglobulin G light chain consists of two domains. In some cases, distinct structural regions of a polypeptide chain are also referred to as domains.

Domains can be isolated by treating the protein with Proteolytic Enzymes, which readily cleave peptide bonds in the polypeptide region located between the domains. Following this Treatment, certain domains may retain their biological properties.