BIOCHEMISTRY - Textbook - Ostapchenko L. I. - 2012

Chapter 5. STRUCTURE, PROPERTIES, AND FUNCTIONS OF PROTEINS

5.2. Protein Structure

5.2.5. Quaternary Structure of Proteins

Many Proteins consist of a single polypeptide chain only. They are referred to as monomers. Monomers also include proteins that comprise several chains connected covalently, such as by Disulfide Bonds (therefore, Insulin should be regarded as a monomeric protein).

At the same time, there are proteins composed of two or more polypeptide chains. Once the three-dimensional Structure of each polypeptide chain is formed, they assemble via the same weak interactions that drive The formation of tertiary structure: hydrophobic, ionic, and Hydrogen Bonds.

The number and spatial arrangement of polypeptide chains are referred to as The quaternary structure of proteins. Individual polypeptide chains in such a protein are called protomers, or subunits. A protein comprising multiple protomers is termed an oligomeric protein.

Oligomeric Proteins can contain anywhere from two to several dozen protomers, although those with two to four polypeptide chains are the most common (dimeric and tetrameric proteins).

For example, the enzyme hexokinase contains 2 protomers; the erythrocyte protein Hemoglobin and the enzyme Lactate dehydrogenase contain 4; the mitochondrial inner membrane enzyme cytochrome c oxidase contains 13; and Glutamine Synthetase contains 12 protomers (Fig. 5.20). There are also large multifunctional complexes comprising several dozen polypeptide chains (for instance, the Pyruvate dehydrogenase complex consists of 312 protomers).

Some oligomeric proteins contain identical protomers (e.g., hexokinase), whereas others consist of distinct protomers. For instance, hemoglobin contains two α- and two β-protomers, whereas lactate dehydrogenase, which possesses 4 protomers, features 2 types of monomers (H and M) that can combine in various ratios depending on the tissue (e.g., 4H or 3H + 1M, etc.).

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Fig. 5.20. Subunit structure of glutamine synthetase

Oligomeric proteins have a high molecular weight. Proteins with a molecular weight exceeding 50,000 Da almost invariably consist of multiple monomeric polypeptide chains. Compared to individual monomeric proteins, oligomers perform more complex Functions.

The recognition and association of individual protomers in an oligomeric protein occur through the formation of contact sites on their surfaces. These sites consist of amino acid residues brought together in a specific region during the Formation of the protein's tertiary structure. The combination of these residues forms unique surfaces capable of binding to one another with high Specificity.

The specificity of binding at contact sites is determined by their complementarity. Complementarity refers to the spatial and chemical correspondence of interacting surfaces. In addition to geometric fit, the Functional groups of amino acid residues on one contact surface must form weak chemical bonds with The amino acid residues on the opposing surface (Fig. 5.21). The region of Contact surfaces typically contains numerous hydrophobic amino acid residues, whose association forms the Hydrophobic core of the oligomeric protein. Hydrophilic residues can form hydrogen and ionic bonds.

Fig. 5.21. Diagram of the formation of a dimeric protein molecule:

A large number of weak bonds, indicated by dashed lines in the figure, are formed between protomers A and B

Thus, the interaction between protomers takes place across numerous points on the contacting surfaces, resulting in the formation of dozens of weak bonds. As a result, contact surfaces associate with high specificity, virtually eliminating any errors in the assembly of the protein's quaternary structure.

Complementarity is a universal principle inherent in living nature, underlying the recognition and association not only of protomers, but also of other (not necessarily protein) molecules.