Protein Denaturation: What is it?

A protein molecule unfolding after being heated

Core Concepts

In this article, you will learn about protein denaturation. Also, you will learn what causes denaturation and its effects on the cellular environment.

Topics Covered in Other Articles

What are proteins?

Proteins are a macromolecule made up of organic compounds called amino acids. Amino acids connect together by peptide bonds and produce polypeptide chains. Additionally, These chains will produce different levels of protein structure: primary, secondary, tertiary and quaternary. These structures then change through a process called denaturation.

Diagram of the different levels of protein structure
Four different levels of Protein Structure
Source: Wikimedia Commons

What is Protein Denaturation?

Denaturation is the process of the modification of the molecular structure of a protein. This involves the breakdown of bonds such as hydrogen bonds and covalent bonds (disulfide bonds (S-S). Proteins generally have a compact globular shape or are “folded” instead of having random structures. Additionally, denaturation can be reversible or irreversible. For example, a fried egg’s proteins can’t return to their original state. Cooling warmed milk consequently causes the proteins in the milk to revert to their original form.

A protein molecule unfolding after being heated (denaturation)
Source: Wikimedia Commons

What happens when a protein is denatured?

When the weak (hydrogen) bonds break, the normal shape of the protein disrupts. Specifically, the secondary and tertiary structure breaks down, leaving an unraveled chain of amino acids. Importantly, denaturation happens by physical and chemical means, such as the following:

MechanicalForces such as agitation or stirring are able to disrupt the structure of a protein by breaking down the weak bonds. For example,  whisking egg whites can create a light foam which can be used in baking.
HeatIncreased temperatures cause kinetic energy to increase as well. This will cause molecules to vibrate quickly and this breaks the bonds, causing the protein structure to unravel.
Acids & BasesAcids and bases can change the pH of the proteins. This will disrupt the hydrogen bonding and also salt bridges. This will lead to the denaturation of the protein structure.
Heavy Metals (Hg2+, Pb2+, Cd2+)The presence of heavy metals can disrupt disulfide bonds in the second and tertiary structures. 
Organic Solvents (alcohols, ketones)Organic solvents will disrupt  the hydrophobic interactions between nonpolar side chains of amino acids

Enzyme Protein Denaturation

Denaturation can affect different types of proteins such as enzymes. An enzyme is a protein that acts as a catalyst for biological processes. All enzymes have a structure called an active site to which reactants called substrates can bind. This reaction then converts the substrates into molecules called products.

Diagram showing the reaction between an enzyme and a substrate
Diagram showing the reaction between an enzyme and a substrate
Source: Wikimedia Commons

When an enzyme is denatured, whether, from temperature changes or the presence of organic solvents, the structure of the enzyme will be disrupted. This then causes the structure to unfold and the substrate will no longer be able to bind to the active site. Therefore, this typically causes a loss of biological activity. A denatured enzyme can regain its functionality and original structure when there are proper conditions are put in place.

Graph showing increased temperatures causing denaturation, causing enzyme activity to decrease
Graph showing increased temperatures causing enzyme activity to decrease
Source: Wikimedia Commons

An example of an important enzyme is pepsin. Pepsin is an enzyme found in the stomach as it aids in the digestion of proteins by breaking them down into smaller peptides. The stomach contains gastric juices (a combination of hydrochloric acid and enzymes) and pepsin thrives in this acidic environment (pH 1.5-2). If the pH of the environment increases (more than pH 6), the enzyme pepsin irreversibly denatures. The denaturation of pepsin causes improper digestion and could lead to stomach infections.

Heat Shock Proteins

Denaturation can also cause biological responses such as heat shock proteins. These proteins are produced by cells in the body when exposed to harsh and stressful conditions. This could be caused by exposure to high temperatures or cold, during the healing of a wound, inflammation, or UV light. These heat shock proteins serve as protection of body cells by keeping their integrity and by keeping signaling pathways functional for the survival of cells. The most studied heat shock proteins are Hsp60, Hsp70, and Hsp90 and this is based on the order of size respectively in kilodaltons (60, 70,90).

Diagram showing functions of Heat Shock Proteins, correctly folding a new protein and a denatured protein
Source: Research Gate
Diagram showing functions of Heat Shock Proteins, correctly folding a new protein and a denatured protein