Core Concepts
In this tutorial, you will learn what makes up protein structure and how factors, like temperature and pH affect a protein’s stability. You will also learn that protein structure and stability are important to a protein’s function.
Topics Covered in Other Articles
- Amino Acid Chart
- Viral Life Cycle
- What is Cell Signaling?
- GPCR – G Protein Coupled Receptors
- Enzymes – Function and Types
- Glycolysis: Let’s break it down!
What are Protein Structure and Stability?
Protein structure describes the specific shape that a protein takes on. Proteins can be very rigid in their structures, very relaxed, or somewhere in between. Chemical interactions, like hydrogen bonds, act like glue to hold these structures together. A protein’s primary amino acid sequence is a big factor in determining which of these chemical interactions can form, and where. Amino acids are bonded together to form peptide bonds, a type of amide bond.
Proteins are dynamic. They are always moving! This could mean small movements, like an atom vibrating, or larger movements, like a protein changing its overall shape. Protein stability is a measure of how well a protein “sits still.” In other words, it is how effectively a protein maintains a specific shape. Proteins can usually assume a few stable shapes. Biochemists continue to be interested in what shapes proteins occupy in biological conditions, like in the cell.
Protein Structure
Why is Protein Structure Important?
There are tens of thousands of proteins found in the human body. They all have different roles, and many are essential to life. What determines their different roles? A protein’s shape is a major factor in how it behaves. For example, hemoglobin has a shape that lets it uptake, carry, and release oxygen in the body. However, the protein Keratin looks nothing like hemoglobin, and cannot carry oxygen. It instead forms strong fibers that make up your hair and nails.
What Determines Protein Structure?
Proteins form Interactions with themselves.
The amino acids that make up proteins have chemical properties that help them hold their shape. For example, in the primary structure of a protein, amino acids are linked together via covalent bonds to form a long and durable chain. Additionally, these amino acids can form other types of interactions, like in the table below, that help them maintain their more complex overall shapes.
Protein structures are built upon some fundamental chemical interactions that act like a glue. These include ionic bonds, hydrogen bonds, Van de Waals forces, and disulfide bonds. The table below is a great introduction to these forces; however, it is not a complete list. For example, amino acids can undergo a more complex contact called pi-stacking.
| Protein Interaction | Explanation |
| Ionic Bonds | Ionic bonds form between atoms or molecules based on charge. Amino acid side chains, or R groups, either have positive charge (like lysine), negative charge (like aspartic acid), or are neutral (like glycine). Positively charged amino acids attract negatively charged amino acids. More generally, positive regions on a protein attract negative regions, forming strong ionic bonds. |
| Hydrogen Bonds | Hydrogen bonds are strong electrostatic interactions that form between a slightly positive hydrogen atom (that is attached to Oxygen, Nitrogen, or Fluorine), and another O, N, or F atom. These are significant interactions for many biological molecules. |
| Van der Waals | Van der Waals, or London dispersion, forces are weak and occur at very close proximity. Although the weakest interaction here, they still play a critical role in maintaining a protein’s structure. |
| Disulfide Bonds | Disulfide bonds are covalent bonds between sulfur atoms, typically found on the amino acid, Cysteine. Also called disulfide linkages, or bridges, they are another way to form connections between amino acids in a protein. |
Interactions with Solvents and Other Molecules.
Proteins use these same types of interactions to form chemical relationships with what is around them. For instance, they interface with different solvents. They also interface with molecules of all shapes and sizes, including other proteins.
In the lab, proteins are exposed to solvents like water or alcohol. They then take on different structures depending on these solvents’ properties. Proteins in alcohol often denature, which means they lose the majority of their structure, but retain their primary sequence of amino acids. Proteins in water exhibit something called the hydrophobic effect.
The Hydrophobic Effect
One of the main molecules proteins interact with is water. Proteins can have hydrophilic, “water-loving,” regions as well as hydrophobic, “water-fearing” regions. When a protein is in an environment that is mostly water, the “water-loving” regions will arrange to face the water. However, the “water fearing” regions will avoid water, and instead interact with themselves. This is called the hydrophobic effect. In most proteins, this is the reason that hydrophobic amino acids are concentrated in the core of the protein, while the hydrophilic regions make up the exterior.
Proteins also from interactions with other proteins. One example is an enzyme found in viruses called reverse transcriptase. It is made up of two proteins in a complex called a dimer (di- meaning “two”). The two proteins in reverse transcriptase depend on each other for their structural stability, and their function.
Protein Stability
Protein structure and stability go hand in hand. The interactions that hold proteins in their shape, like hydrogen bonds, can be affected by many factors. These include solvent, pH, salinity (how much salt is present), temperature, and the presence of other molecules. The tables below introduce these factors.
Solvent, pH, and Salinity
| Factor | Explanation |
| Solvent | Solvent can contain a variety of properties, all of which affect a protein’s structure. Solvents with alcohol (-OH) can form and disrupt hydrogen bonds in a protein structure. The solvent water promotes the hydrophobic effect. |
| pH | pH determines whether an amino acid acts as an acid, a base, or a neutral species. This affects the charge of the amino acid (and the charge of the overall protein). A change in pH can disrupt connections that are reliant on the charge, like electrostatic interactions. When amino acids undergo acid/base chemistry, they are also gaining or losing protons, so pH can also disrupt connections reliant on hydrogens, like hydrogen bonding. |
| Salinity | Salinity is a measure of how much salt is present in your solution and not just NaCl. A low level of salt is usually helpful to protein folding because the salt’s ions can help to stabilize the charges on amino acids. However, high levels of salt can disrupt interactions a protein needs to fold. |
Temperature and Other Molecules
| Factor | Explanation |
| Temperature | High temperatures will also disrupt the interactions that hold together a protein structure. Proteins are commonly stable at lower temperatures. For example, this is taken advantage of in protein imaging methods like Cryogenic Election Microscopy (Cryo-EM). |
| Molecules | This more general category includes proteins, small signaling molecules, and even salts. Proteins may rely on other proteins for their stability, like in the case of reverse transcriptase. They may also rely on other proteins for folding, cell transport, signaling, and other functions. This is often accompanied by a change in protein(s) shape. Small signaling molecules can affect the chemistry in a small region of the protein, which can result in protein structure changes of various impacts. |