ArticleProceedings of the National Academy of Sciences of the United States of America2015
Distinct activation of an E2 ubiquitin-conjugating enzyme by its cognate E3 ligases.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Fluorophore placement and size impact E2 ubiquitination efficiency.The Biochemical journal · 2026Article
- The Hrd1-Mediated ERAD Pathway in Plants: Conserved Principles and Plant-Specific Innovations.International journal of molecular sciences · 2026Review
- Structure-guided analysis and prediction of human E2-E3 ligase pairing specificity.bioRxiv : the preprint server for biology · 2026Article
- Endoplasmic Reticulum-Associated Protein Degradation.Cold Spring Harbor perspectives in biology · 2022Review
- Elements of the ERAD ubiquitin ligase Doa10 regulating sequential poly-ubiquitylation of its targets.iScience · 2022Article
- A positive genetic selection for transmembrane domain mutations in HRD1 underscores the importance of Hrd1 complex integrity during ERAD.Current genetics · 2022Article
- The Role of Conformational Dynamics in the Recognition and Regulation of Ubiquitination.Molecules (Basel, Switzerland) · 2020Review
- Who with whom: functional coordination of E2 enzymes by RING E3 ligases during poly-ubiquitylation.The EMBO journal · 2020Article
- Unstructured Biology of Proteins from Ubiquitin-Proteasome System: Roles in Cancer and Neurodegenerative Diseases.Biomolecules · 2020Article
- The Ubiquitin Conjugating Enzyme: An Important Ubiquitin Transfer Platform in Ubiquitin-Proteasome System.International journal of molecular sciences · 2020Review
- Putative Interaction Proteins of the Ubiquitin Ligase Hrd1 inEvolutionary bioinformatics online · 2018Article
- Conformational Dynamics Modulate Activation of the Ubiquitin Conjugating Enzyme Ube2g2.ACS omega · 2017Article
- Crystal Structure of a Ube2S-Ubiquitin Conjugate.PloS one · 2016Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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 mutant Ubc7 was restored selectively by the Hrd1 RING domain but not by the Doa10 RING domain. In agreement with the in vitro data, Ubc7 α2 helix mutations selectively impaired the in vivo degradation of Doa10 substrates but had no apparent effect on the degradation of Hrd1 substrates. To our knowledge, this is the first example of distinct activation requirements of a single E2 by two E3s. We propose a model in which the RING domain activates Ub transfer by stabilizing a transition state determined by noncovalent interactions between the α2 helix of Ubc7 and Ub and that this transition state may be stabilized further by some E3 ligases, such as Hrd1, through additional interactions outside the RING domain.
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