USP14-regulated allostery of the human proteasome by time-resolved cryo-EM.

ABSTRACT: Proteasomal degradation of ubiquitylated proteins is tightly regulated at multiple levels^1-3. A primary regulatory checkpoint is the removal of ubiquitin chains from substrates by the deubiquitylating enzyme ubiquitin-specific protease 14 (USP14), which reversibly binds the proteasome and confers the ability to edit and reject substrates. How USP14 is activated and regulates proteasome function remain unknown^4-7. Here we present high-resolution cryo-electron microscopy structures of human USP14 in complex with the 26S proteasome in 13 distinct conformational states captured during degradation of polyubiquitylated proteins. Time-resolved cryo-electron microscopy analysis of the conformational continuum revealed two parallel pathways of proteasome state transitions indu

SUBMITTER: Zhang S 

PROVIDER: S-EPMC9117149 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature