Proteins are fundamental to life. They are involved in virtually every process within our bodies, from catalyzing chemical reactions to defending against diseases.
What makes these molecules so versatile is not just their chemical composition, but also their three-dimensional shape. The process by which a protein assumes its functional shape is called protein folding, and it’s a critical part of life at the molecular level.
Proteins are made up of long chains of amino acids. These chains are like beads on a string, but unlike a simple string of beads, proteins don’t remain in a straight line. Instead, they twist and turn, folding into complex shapes.
When a protein is being formed, it starts as a linear chain of amino acids created by the ribosomes in a cell. As this chain grows, it begins to fold into its final shape. The amino acids interact with each other through various chemical forces, and these interactions guide the folding process. Some parts of the chain might be attracted to each other, while other parts repel each other, causing bends and twists.
There are four levels of protein structure: primary, secondary, tertiary and quaternary. The primary structure is the sequence of amino acids, which is like the order of letters in a word. The secondary structure involves local folding patterns, such as helices or pleated sheets, created by hydrogen bonding between parts of the amino acid chain. The tertiary structure is the overall 3D shape of the entire protein, formed by a variety of interactions, such as hydrophobic forces, hydrogen bonds and disulfide bridges. Finally, the quaternary structure applies to proteins made of multiple chains, where these chains come together in a larger assembly.
Why is protein folding so important? The function of a protein is directly related to its shape. If a protein folds correctly, it will function as it’s supposed to. But if it folds incorrectly, bad things can happen. Diseases like Alzheimer’s, Parkinson’s and mad cow disease are associated with misfolded proteins, which can clump together in ways that harm cells.
Moreover, protein folding doesn’t happen in isolation. Inside cells there are specialized molecules called chaperones that help proteins fold correctly. These chaperones ensure that proteins don’t get stuck in the wrong shape during the folding process. Without these helpers, many proteins would fail to reach their functional form, leading to cellular problems.
Scientists are still learning about the mysteries of protein folding. It’s an incredibly complex process that involves many factors, and even small changes can have major impacts. Until recently, attempts to predict the shape of a folded protein from the amino acid sequence were unsuccessful because there are nearly an infinite number of ways to fold the resulting structure. A polypeptide is very flexible, with the ability to rotate in multiple ways at each amino acid. For a protein with 100 amino acids and only three possible rotations, the number of possible folds is greater than the total number of atoms in the known universe. Recent advances in AI have led in some cases to successful folding.
Understanding protein folding is important not only for biology, but also for medicine, where researchers are exploring ways to correct misfolded proteins to treat diseases. While the idea of a chain of amino acids folding into a working protein might seem simple, it’s a finely tuned process. The folded structure is what allows proteins to carry out the countless functions necessary for life. In many ways the secret to understanding life itself may be hidden in the twists and turns of protein folding.
Richard Brill is a retired professor of science at Honolulu Community College. His column runs on the first and third Fridays of the month. Email questions and comments to brill@hawaii.edu.
