Protein Chemistry. Structure, Properties, Research Methods - Shendryk A.N. 2022

Protein Structure
Three-Dimensional Protein Structure
Quaternary Protein Structure

Quaternary Structure is characteristic only of Proteins that exist as aggregates of two or more peptide chains linked together by non-covalent interactions. Covalent bonds, including disulfide bridges, are absent. Proteins of this type are called oligomers. These can be dimers, trimers, and so on. Below, as an example, the figure shows models of the structures of Insulin and Hemoglobin determined by X-ray crystallography (the figures are taken from the Protein Data Bank via the Internet).

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Oligomeric Proteins with A large number of peptide chains are also known.

If the peptide chains making up the oligomer are identical, it is called homogenous; if the chains are non-identical, it is heterogeneous. The stabilization of aggregates is carried out mainly through electrostatic and Hydrogen Bonds between side chains located On the surface of individual peptide chains. Hydrophobic interactions may occur, but their significance is small since most nonpolar residues are located inside each globular subunit.

Among oligomeric proteins, hemoglobin—a heterogeneous tetramer—is the most thoroughly studied. Its Tertiary and Quaternary structures have been determined using X-ray crystallography. The successful resolution of this problem was the result of painstaking research spanning 25 years, carried out by Perutz and his colleagues in Cambridge. Simultaneously and in parallel, Myoglobin was also investigated by X-ray crystallography in the same laboratory.

The hemoglobin molecule consists of two identical α-chains and two β-chains. Each chain, together with the heme group, is very similar to the myoglobin molecule. Each of the 4 chains is folded in an irregular manner and consists of a series of α-helical regions separated by bends. Similar to myoglobin, the α- and β-chains of hemoglobin contain about 70% α-helical regions.

In terms of tertiary structure, the α- and β-chains are very close. They consist of α-helical regions of equal length, bent at equal angles and in the same directions. In addition, both chains of hemoglobin have a tertiary structure very similar to that of myoglobin. This similarity is attributed to a significant number of identical amino acid residues at key positions in the peptide chain.

Many oligomeric proteins dissociate into subunits at high and low pH values, as well as under the action of high concentrations of urea or salts.

Oligomeric proteins denature in two stages:

> The First stage is dissociation into subunits (individual chains);

> the second is the unfolding (Denaturation) of individual chains.

Oligomeric proteins possess the capacity for self-assembly. For example, in a mixture containing α- and β-chains under favorable conditions, the self-assembly of hemoglobin takes place. This fact indicates that all the Structural Features of secondary, tertiary, and quaternary structures are encoded in the Amino Acid Sequence (Primary Structure) of proteins. One of the distinctive Features of oligomeric proteins is their ability to exhibit a cooperative effect.

Let us examine The Essence of the cooperative effect using a specific example. We will compare the processes of oxygen saturation in molecules of myoglobin (a single-chain protein lacking quaternary structure) and hemoglobin, an oligomeric protein. The experimental oxygen saturation curves for these two proteins differ significantly from each other (see Fig. 2.4).

Fig. 2.4 Oxygen absorption curves for Myoglobin and hemoglobin

The saturation curve for myoglobin is characteristic of the binding of a single Ligand. A sigmoidal curve is characteristic of proteins with multiple peptide chains. In this case, a positive cooperative effect is manifested. A similar phenomenon can be observed in proteins with various Functions.

Qualitatively, positive cooperativity can be described as follows. The initial binding of one ligand in an oligomeric protein molecule facilitates the binding of the second ligand to that molecule, followed by the third, the fourth, and so on. In hemoglobin, specifically, the binding of an O₂ molecule to the first heme group facilitates the binding of oxygen to the second, third, and fourth Hemes.

The cooperative link between subunits in an oligomeric protein molecule is based on allostery. The essence of allostery is that protein molecules are capable of adopting different spatial Conformations with varying activities. The Importance of this protein property is very great. A large number of Enzymes that control regulatory functions (functions ensuring the maintenance of required reaction rates) belong to the class of oligomeric proteins.