The unique three-dimensional structure of a polypeptide is its tertiary structure (see image below). This structure is in part due to chemical interactions at work on the polypeptide chain. Primarily, the interactions among R groups creates the complex three-dimensional tertiary structure of a protein.
The nature of the R groups found in the amino acids involved can counteract the formation of the hydrogen bonds described for standard secondary structures. For example, R groups with like charges are repelled by each other and those with unlike charges are attracted to each other (ionic bonds).
When protein folding takes place, the hydrophobic R groups of nonpolar amino acids lay in the interior of the protein, whereas the hydrophilic R groups lay on the outside. We refer to the former types of interactions as hydrophobic interactions. Interaction between cysteine side chains forms disulfide linkages in the presence of oxygen, the only covalent bond forming during protein folding.
All of these interactions, weak and strong, determine the final three-dimensional shape of the protein. When a protein loses its three-dimensional shape, it may no longer be functional.
In nature, some proteins are formed from several polypeptides, also known as subunits, and the interaction of these subunits forms the quaternary structure. Weak interactions between the subunits help to stabilize the overall structure. For example, insulin (a globular protein) has a combination of hydrogen bonds and disulfide bonds that cause it to be mostly clumped into a ball shape.
Insulin starts out as a single polypeptide and loses some internal sequences in the presence of post-translational modification after the formation of the disulfide linkages that hold the remaining chains together. Silk (a fibrous protein), however, has a β-pleated sheet structure that is the result of hydrogen bonding between different chains.
The illustration below shows the four levels of protein structure (primary, secondary, tertiary, and quaternary).
Denaturation and Protein Folding
Each protein has its own unique sequence and shape that are held together by chemical interactions. If the protein is subject to changes in temperature, pH, or exposure to chemicals, the protein structure may change. This could result in the protein losing its shape without losing its primary sequence. We refer to this phenomenon as denaturation.
Reversible and Irreversible Denaturation
Denaturation is often reversible. This is because the primary structure of the polypeptide is conserved in the process if the denaturing agent is removed, allowing the protein to resume its function. Sometimes denaturation is irreversible, leading to loss of function. One example of irreversible protein denaturation is when an egg is fried. The albumin protein in the liquid egg white is denatured when placed in a hot pan (see image below).
Not all proteins are denatured at high temperatures. For instance, bacteria that survive in hot springs have proteins that function at temperatures close to boiling. The stomach is also very acidic, has a low pH, and denatures proteins as part of the digestion process. However, the digestive enzymes of the stomach retain their activity under these conditions.
Is denatured protein still good?
The peptide bonds that are present in protein are broken. However, despite the change in the structure of the protein, denatured protein still contains all of the amino acids that are found in other forms of the protein. As a result, denatured proteins are still nutritionally beneficial.
Protein folding is critical to its function. It was originally thought that the proteins themselves were responsible for the folding process. Only recently was it found that often they receive assistance in the folding process from protein helpers that associate with the target protein during the folding process. We refer to this protein helpers as known as chaperones (or chaperonins). They act by preventing aggregation of polypeptides that make up the complete protein structure, and they disassociate from the protein once the target protein is folded.
Video Summary of Proteins
Proteins play countless roles throughout the biological world, from catalyzing chemical reactions to building the structures of all living things.
Despite this wide range of functions all proteins are made out of the same twenty amino acids, but combined in different ways. The way these twenty amino acids are arranged dictates the folding of the protein into its unique final shape. Since protein function is based on the ability to recognize and bind to specific molecules, having the correct shape is critical for proteins to do their jobs correctly.
The video below by RCSB Protein Data Bank explores the about the 3D shape, structure and function of proteins.