What Are Protein Side Chains and Why Are They Important?

Proteins perform a vast array of tasks within living organisms and are assembled from smaller units called amino acids. While every amino acid shares a common foundation, each is distinguished by a unique chemical group known as a side chain. The specific properties of this side chain are what determine how a protein is built and how it ultimately functions.

What Are Protein Side Chains?

Every amino acid has a consistent core structure built around a central carbon atom, known as the alpha-carbon. This carbon is bonded to four components: a positively charged amino group, a negatively charged carboxyl group, a hydrogen atom, and a fourth variable group. This fourth component, the side chain, is what makes each amino acid distinct.

This fourth group is the side chain, often represented by the letter ‘R’ in diagrams to signify its variable nature. While the backbone of amino acids is constant, the side chain differs in size, shape, and chemical properties among the 20 common amino acids. This variability gives each amino acid its unique identity.

Think of the amino acid backbone as a standard link in a chain and the side chain as a unique charm attached to it. A protein is a long chain of these links. The specific sequence and combination of these “charms” determine the protein’s overall structure and its job in the body.

Types of Protein Side Chains

The 20 common amino acid side chains are sorted into categories based on their chemical properties. These properties, determined by the atoms in the side chain, dictate how they interact with their surroundings, and particularly with water.

Nonpolar, or hydrophobic, side chains are largely composed of carbon and hydrogen atoms that do not interact well with water. Amino acids like valine and leucine have nonpolar side chains. They tend to be pushed away from water and are often found clustered in the interior of a protein.

Polar but uncharged side chains contain atoms like oxygen or nitrogen that can form hydrogen bonds with water, making them soluble. Serine and threonine are examples with polar side chains. Their ability to interact with water means they are commonly located on the surface of proteins.

Electrically charged side chains can be either acidic or basic. Acidic side chains, like those of aspartic acid and glutamic acid, carry a negative charge. Basic side chains, such as in lysine and arginine, carry a positive charge, and these charged groups can form strong ionic bonds.

Side Chains and Protein Structure

A protein’s final three-dimensional shape is a direct result of interactions between its amino acid side chains. After an amino acid chain is built, it folds into a specific, stable conformation based on the chemical properties of its R-groups. Several types of interactions work together to stabilize this structure:

• The hydrophobic effect: Nonpolar, water-repellent side chains are driven to the core of the protein, creating a compact structure.
• Hydrogen bonds: These form between different polar uncharged side chains or between side chains and the polypeptide backbone.
• Ionic bonds: Also known as salt bridges, these attractions form between positively and negatively charged side chains, locking parts of the protein together.
• Disulfide bonds: This special covalent bond can form between the side chains of two cysteine amino acids, acting like a molecular staple to add stability.

Side Chains and Protein Function

A protein’s function depends on its three-dimensional structure and the chemical properties of the side chains on its surface. The precise arrangement of these R-groups creates specialized regions that interact with other molecules with a high degree of specificity.

Enzymes, proteins that accelerate chemical reactions, have an active site formed by a specific arrangement of side chains. This pocket creates a chemical environment tailored to bind specific molecules, called substrates. Once bound, the side chains can participate directly in the reaction by donating or accepting protons to help break or form chemical bonds.

Receptor proteins have binding sites on their surfaces made of particular side chains. These sites are shaped to recognize and bind specific signaling molecules, like hormones or neurotransmitters. This binding event triggers a change in the receptor’s shape, which transmits a signal inside the cell.

A mutation in DNA can cause the wrong amino acid to be incorporated into a protein. If this new amino acid has a side chain with different properties, such as replacing a nonpolar side chain with a charged one, it can disrupt folding. This alters the protein’s structure and can abolish its function, which is an underlying cause of many diseases.