Deciphering the Dynamic Structure and Function of the 26S Proteasome Complex Upon Oxidative Stress

摘要

Reactive oxygen species (ROS) can induce oxidative stress, which leads to oxidation of the side chains of amino acids, protein cross-linking, and protein fragmentation. Most of oxidative modifications lead to disruption of protein structure and an impaired functionality. The accumulation and aggregation of oxidatively damaged proteins is implicated in neurodegenerative diseases and aging. In consequences, these oxidized proteins have to be removed in order to prevent serious metabolic disturbance. The proteasomal degradation pathway is the major proteolytic system responsible for the removal of oxidized proteins. However, the oxidative stress-dependent regulation of the 26S proteasome remains largely unknown. Therefore, we intend to unravel proteomic changes in the 26S proteasome to understand how the 26S proteasome proteolytic activity is modulated in response to oxidative stress.