Characterization of Interaction Between Pathogenic PolyQ Proteins and Q-rich Target Proteins

Abstract

To understand the pathogenesis of many diseases attributed to protein toxicity such as polyglutamine (polyQ) diseases, it is very crucial to determine how these toxic disease proteins interact and trap their numerous targets. However, in polyQ diseases, details of required features for their interaction with targets remain largely unknown. Here, we identified what features are necessity for interaction between polyQ and targets, and how target proteins have an effect on polyQ aggregate formation. We visualized the interaction between pathogenic polyQ proteins and Q-rich possible target proteins in neurons, which is predicted on the Q-Q based protein interaction occurring in pathogenic polyQ-containing proteins for their self-oligomerization/aggregation. Furthermore, we checked whether the interaction of pathogenic polyQ proteins with targets can be modulated through designed strategies such as using a structural inhibitor molecule. Through this study, we established the model system to study the modes of interaction between pathogenic polyQ and Q-rich target proteins and aim to prove the possibility of target proteins accelerating aggregate formation by acting as glue. ⓒ 2016 DGIST