|Figure 3.10 Primary Structure Specifies Tertiary Structure
Protein folding plays a critical role in protein function, and a key discovery regarding the nature of protein structure was made by Anfinsen and colleagues in the 1960’s. In one of the most critical experiments contributing to this discovery, Haber and Anfinsen denatured a protein, the ribonuclease (RNase) enzyme, and then allowed it to refold. The researchers predicted that if the protein folding structure is innate to the amino acid sequence of the protein, then the final product should be the same as the initial RNase. To conduct this experiment, the researchers denatured RNase with the chemicals urea and mercaptoethanol. When these chemicals were removed and the protein was allowed to reform tertiary structures, products identical to the original RNase were formed. Thus, Haber and Anfinsen concluded that the tertiary structure of a protein is determined by its primary structure. For this important discovery, Anfinsen was awarded the 1972 Nobel Prize in chemistry. A corollary to this discovery is that there are specific proteins called chaperones that assist in proper protein folding. More recently, scientists have identified incorrect protein folding as the cause of various diseases, including Alzheimer’s disease, cystic fibrosis, and many cancers. In diseases such as Alzheimer’s, amyloid precursor proteins stick together during the process of folding, creating plaques that cause the disease. However, with cystic fibrosis the disease is not a direct result of improper protein folding; rather, it is due to an insufficient amount of properly folded protein. It is thought that many cancers result from a similar problem. When the cell division inhibitory protein p53 becomes incorrectly folded, unchecked cell division leads to tumor formation. Given the importance of protein folding in many diseases, the development of medical treatments that target protein folding is currently an active area of research.
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