The stability of a protein depends on its environment as well as the exposure to conditions that can promote chemical deterioration or conformational changes.
If the protein is subject to changes in temperature, pH, or exposure to chemicals, the internal interactions between the protein’s amino acids can be altered, which in turn may alter the shape of the protein. Although the amino acid sequence (also known as the protein’s primary structure) does not change, the protein’s shape may change so much that it becomes dysfunctional, in which case the protein is considered denatured. In the cell, proteins called chaperones facilitate the proper folding and stability of proteins.
It is often possible to reverse denaturation because the primary structure of the polypeptide, the covalent bonds holding the amino acids in their correct sequence, is intact. Once the denaturing agent is removed, the original interactions between amino acids return the protein to its original conformation and it can resume its function. However, denaturation can be irreversible in extreme situations, like frying an egg. The heat from a pan denatures the albumin protein in the liquid egg white and it becomes insoluble. The protein in meat also denatures and becomes firm when cooked.
Proteins largely function in an aqueous environment. Therefore, hydrophobic interactions are important in imparting stability to a protein. This process involves amino acids with nonpolar, hydrophobic R groups clustering together on the inside of the protein away from water, leaving hydrophilic amino acids on the outside to interact with surrounding water molecules.
However, a folded protein has an overall lower entropy. This is balanced out by the increase of entropy of the surrounding water molecules (solvation layer) upon protein folding. Hydrophobic interactions would decrease the possible conformations of water molecules. So by sequestering the hydrophobic R groups away from water upon protein folding, it increases the water’s entropy. This balances out the loss of entropy from folding the protein.
Protein folding, and therefore stability, is driven primarily by entropy.
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Key Points
• Proteins change their shape and may become dysfunctional (denatured) when exposed to different chemicals, pH, or temperatures.
• Chaperones are proteins that facilitate folding of other proteins, and prevent denaturation and aggregation.
• Some proteins can refold after denaturation while others cannot.
• Hydrophobic interactions and the increase of entropy in the solvation layer is important for a folded protein’s stability
Key Terms
denaturation: the change of folding structure of a protein (and thus of physical properties and function) caused by heating, changes in pH, or exposure to certain chemicals
chaperones: a class of proteins that facilitate folding and proper conformation of other proteins
hydrophobic interactions: amino acids with nonpolar, hydrophobic R groups cluster together on the inside of the protein, leaving hydrophilic amino acids on the outside to interact with surrounding water molecules
solvation layer: water molecules around the protein; the sequestering of hydrophobic amino acids away from water increases the entropy of the solvation layer