Specific lid-base contacts in the 26s proteasome control the conformational switching required for substrate degradation.

ABSTRACT: The 26S proteasome is essential for proteostasis and the regulation of vital processes through ATP-dependent degradation of ubiquitinated substrates. To accomplish the multi-step degradation process, the proteasome's regulatory particle, consisting of lid and base subcomplexes, undergoes major conformational changes whose origin is unknown. Investigating the Saccharomyces cerevisiae proteasome, we found that peripheral interactions between the lid subunit Rpn5 and the base AAA+ ATPase ring are important for stabilizing the substrate-engagement-competent state and coordinating the conformational switch to processing states upon substrate engagement. Disrupting these interactions perturbs the conformational equilibrium and interferes with degradation initiation, while later processing steps

SUBMITTER: Greene ER 

PROVIDER: S-EPMC6910829 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature