Substrate-engaged 26S proteasome structures reveal mechanisms for ATP-hydrolysis-driven translocation.

ABSTRACT: The 26S proteasome is the primary eukaryotic degradation machine and thus is critically involved in numerous cellular processes. The heterohexameric adenosine triphosphatase (ATPase) motor of the proteasome unfolds and translocates targeted protein substrates into the open gate of a proteolytic core while a proteasomal deubiquitinase concomitantly removes substrate-attached ubiquitin chains. However, the mechanisms by which ATP hydrolysis drives the conformational changes responsible for these processes have remained elusive. Here we present the cryo-electron microscopy structures of four distinct conformational states of the actively ATP-hydrolyzing, substrate-engaged 26S proteasome. These structures reveal how mechanical substrate translocation accelerates deubiquitination

SUBMITTER: de la Pena AH 

PROVIDER: S-EPMC6519459 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature