Protein tertiary structure refers to the three dimensional shape of a protein. The tertiary structure will possess a single polypeptide chain “backbone” with one or more protein secondary structures, i.e. the protein domains. Amino acid side chains might interact and form bonds in a number of ways. The interactions and bonds of side chains within a particular protein helps in determining its tertiary structure. The atomic coordinates define the protein tertiary structure. These coordinates may represent either to a protein domain or to the entire tertiary structure. A number of tertiary structures gets folded into a quaternary structure. 

Overview of Tertiary Structure

The science of the tertiary structure of proteins has emerged from one of hypothesis to one of detailed definition. However Emil Fischer had previously suggested that proteins were made of polypeptide chains and amino acid side chains, it was Dorothy Maud Wrinch who incorporated the geometry into the prediction of protein structures. Wrinch was able to demonstrate this with the help of Cyclol model, the first prediction of the structure of a globular protein. Many other methods were also able to determine, without predicting tertiary structures to within 5 Å (0.5 nm) for small proteins (<120 residues) and, under desirable conditions, confident secondary structure predictions.

Interactions among polar, nonpolar, acidic, and basic R groups within the polypeptide chain produces the complex three-dimensional tertiary structure of a protein. Whenever protein folding takes place in the aqueous environment of the body, the hydrophobic R groups of the nonpolar amino acids mainly lie in the interior of the protein, whereas the hydrophilic R groups lie on the outside. Cysteine side chains form disulfide linkages when oxygen is present, it is the only covalent bond forming during protein folding. Each and every  interaction, weak and strong, helps in determining the final three-dimensional shape of the protein. When a protein loses its three-dimensional shape, it will no longer be known as functional.

Protein Stability

Due to the presence of the weak interactions that control the three-dimensional structure, proteins themselves are very sensitive molecules. The word native state is used here, to define the protein in its most stable natural conformation (i.e. in situ). Variety of external stress factors including temperature, pH, removal of water, presence of hydrophobic surfaces, presence of metal ions and high shear are able to destroy this native state. The loss of secondary, tertiary or quaternary structure due to exposure to a stress factor is known as denaturation. Denaturation is a result of unfolding of the protein into a random or misfolded shape.

A denatured protein can possess quite a different activity profile than the protein in its original state, generally losing biological function. In addition to becoming denatured, proteins are also able to form aggregates under specific stress conditions. Aggregates are often produced at the time of manufacturing process and are basically undesirable, largely because of the possibility of them resulting in adverse immune responses when administered.

In addition to these physical forms of protein degradation, it is also very important to be aware of the possible pathways of protein chemical degradation. These may include oxidation, peptide-bond hydrolysis, deamidation, disulfide-bond reshuffling and cross-linking. The methods used in the processing and the formulation of proteins, involving any lyophilization step, should be carefully examined to prevent any further degradation and to increase the stability of the protein biopharmaceutical both in storage and at the time of drug delivery.

Difference Between Secondary and Tertiary Structure of Protein

Definition

The secondary structure of a protein represents the folding of the peptide chain into an α-helix or β-sheet while the tertiary structure represents the three-dimensional structure of a protein. This explains the basic difference between secondary and tertiary structure of protein.

Shape

As said in the definition, the secondary structure of a protein may be either an α-helix or β-sheet whereas the tertiary structure of a protein is globular. 

Bonds

Secondary structure of a protein possesses hydrogen bonds whereas the tertiary structure of a protein possesses disulfide bridges, salt bridges, and hydrogen bonds. This is another major difference between secondary and tertiary structure of protein.

Examples

The Secondary structure of proteins helps in the formation of collagen, elastin, actin, myosin, and keratin-like fibers whereas the tertiary structure of proteins comprises enzymes, hormones, albumin, globulin, and hemoglobin.

Functions in the Cell

Their functions are yet another important difference between the secondary and tertiary structure of protein. But the secondary structure of proteins is involved in the formation of structures like those of cartilages, ligaments, skin, etc. Whereas tertiary structure of proteins is involved in the metabolic functions of the body.

Conclusion

Tertiary structure of protein is globular and it is formed by the formation of disulfide and salt bridges. It plays a significant role in  metabolism. The difference between secondary and tertiary structure of proteins is based on their structure, bonds, and the role in the cell. Here we come to an end of the topic, we hope that you were able to grasp a clear concept of the tertiary protein structure.