Protein Denaturation

Denaturation disrupts the weak, non-covalent interactions that stabilize a protein’s native conformation. These include hydrogen bonds, hydrophobic interactions, and ionic bonds. For example, heat increases the kinetic energy of atoms, causing vibrations that break these weak bonds. Extreme pH alters the protonation state of acidic and basic amino acid side chains, disrupting salt bridges and hydrogen bonds. Organic solvents can disrupt the hydrophobic core that is crucial for the stability of many globular proteins. In some cases, denaturation is reversible; if the denaturing agent is removed and conditions are returned to physiological normes, some proteins can spontaneously refold into their native state, a process called renaturation, as demonstrated in Anfinsen’s experiments. However, for many proteins, especially large ones, denaturation is irreversible, often leading to aggregation where the unfolded hydrophobic regions stick together non-specifically. This aggregation is a hallmark of several neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease.

Understanding denaturation is critical in both biology and biotechnology. It explains why organisms must maintain a stable internal environment (homeostasis) and is a key consideration in the purification, storage, and handling of protein-based drugs and enzymes to maintain their activity.