Penn State Researchers Discover Misfolded Proteins Evade Cellular Quality Control, Impacting Disease Research
Scientists at Penn State University have identified a new class of protein misfolding where proteins with a specific entangled structure are more prone to misfold. While cellular quality control mechanisms tag many of these misfolded proteins for degradation, nearly half still manage to evade this system. This evasion allows misfolded proteins to accumulate within cells, potentially disrupting protein homeostasis and contributing to aging and diseases like Alzheimer's and Huntington's. The research, led by Ed O’Brien, professor of chemistry, and Yang Jiang, associate research professor of chemistry, utilized existing databases of tagged proteins and protein structures to analyze the proportion of entangled proteins marked for degradation in human fibroblast cells. They found that entangled proteins were 93% more likely to be tagged for removal than non-entangled proteins, with some being tagged even during their formation. Computer simulations further showed that tagged entangled proteins were four times m... 
