Distinct activation of an E2 ubiquitin-conjugating enzyme by its cognate E3 ligases.

ABSTRACT: A significant portion of ubiquitin (Ub)-dependent cellular protein quality control takes place at the endoplasmic reticulum (ER) in a process termed "ER-associated degradation" (ERAD). Yeast ERAD employs two integral ER membrane E3 Ub ligases: Hrd1 (also termed "Der3") and Doa10, which recognize a distinct set of substrates. However, both E3s bind to and activate a common E2-conjugating enzyme, Ubc7. Here we describe a novel feature of the ERAD system that entails differential activation of Ubc7 by its cognate E3s. We found that residues within helix α2 of Ubc7 that interact with donor Ub were essential for polyUb conjugation. Mutagenesis of these residues inhibited the in vitro activity of Ubc7 by preventing the conjugation of donor Ub to the acceptor. Unexpectedly, Ub chain formation by

SUBMITTER: Cohen I 

PROVIDER: S-EPMC4343096 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature