Oligomeric Proteins and Protomer Interaction
Many proteins in the human body and other living organisms function not as single chains, but as complex assemblies. Proteins composed of multiple polypeptide chains are called oligomeric. Each individual polypeptide chain within such a complex is termed a protomer.
The number of protomers in a molecule can vary greatly. For example, a hemoglobin molecule contains 4 protomers, the enzyme aspartate aminotransferase consists of 12, and the tobacco mosaic virus protein includes as many as 2,120 subunits. Because of this architecture, oligomeric proteins always have a high molecular weight.
The interaction between protomers occurs due to strict complementarity of their contacting surfaces. They connect via numerous weak non-covalent bonds:
- Hydrophobic interactions;
- Ionic bonds;
- Hydrogen bonds.
In essence, the interaction of one protomer with others can be viewed as a classic special case of a protein–ligand system, where each protomer acts as a specific ligand for its neighbor. Depending on their composition, oligomers are divided into homodimers (consisting of identical protomers) and heterodimers (containing structurally distinct subunits).
Functional Sites of Heterodimers
If a protein consists of different protomers, binding sites with distinct spatial structures are formed on its surface. The classical architecture of a dimeric protein involves two main subunits, each performing a specific task.
- The active site is located on one of the subunits. Its main task is to bind a specific ligand. It is through this binding that the primary, basic function of the protein is manifested.
- The allosteric (regulatory) site is located on another protomer, spatially separated from the active site. It is designed to bind a special substance—an allosteric ligand (effector). This site does not participate in the basic function, but strictly controls its intensity.
Allosteric Regulation and the Cooperative Effect
The ability to undergo allosteric regulation (i.e., regulation via binding of various ligands) is a key property of oligomeric proteins and proteins with a pronounced domain architecture. This very property fundamentally distinguishes them from simple monomeric proteins (e.g., the difference between oligomeric hemoglobin and monomeric myoglobin).
The mechanism of allosteric regulation operates as follows:
- An effector interacts with the allosteric site.
- Due to the high conformational lability of the protein, this binding immediately induces conformational changes throughout the entire oligomer structure.
- This spatial rearrangement affects the affinity of the active site for its specific ligand.
- As a result, the protein function is either enhanced or suppressed.
Substances that enhance protein function are called activators, while those that depress it are called inhibitors.
A critical consequence of the quaternary structure is the cooperative effect. This is a phenomenon where the interaction of an oligomeric protein with even a single ligand induces cooperative (concerted) changes in the conformation and function of all protomers within the molecule.