Chaperoning Adolescent Proteins

At first glance, proteins appear to be unremarkable strings of amino acids. But the thing about strings is that there are infinite ways to fold them in three-dimensional space, which is how proteins acquire countless conformations that allow them to do everything from catalyzing chemical reactions to mediating cell signaling and fighting infections. Each protein is synthesized linearly, but ends up in a unique “fold” upon which its functionality depends. So how do our cells make sure that the all-important protein folding is conducted correctly?

Many proteins are perfectly capable of folding properly by themselves. But for others folding is trickier because left to their own devices, amino acids are liable to interact with each other in ways that yield misfolded proteins. To prevent this undesired outcome, cells produce a special kind of proteins called chaperones. Chaperones, the bane of high school dance participants, used to be common in the olden days, when gentleman callers who wished to acquaint themselves with a young lady would have to put up with her aging aunt following them around the park. As a chaperone, the aunt’s job was to make sure nothing improper happened, and that is precisely what protein chaperones do when they bind to amino acids and prevent them from interacting prematurely while the protein is folding. Intriguingly, some newly synthesized proteins enter little barrel-shaped chaperones, which are then closed with tiny caps. The proteins undergo folding inside these chaperones and later pop out fully folded!

What happens to unfolded proteins when chaperone activity is disrupted? If chaperones aren’t there to help them reach their functional folds, are proteins condemned to be useless molecular noodles? Yes, but as it turns out, that’s not the worst of it! Misfolded proteins tend to accumulate, forming protein aggregates. When these aggregates form in the brain, they can cause a number of neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease. In fact, studies have revealed that various chaperones are downregulated or dysfunctional in individuals suffering from Parkinson’s disease, indicating that chaperones play a vital role in maintaining the brain’s health.