Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

Who with whom: functional coordination of E2 enzymes by RING E3 ligases during poly-ubiquitylation

[img]
Preview
PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
1MB
[img] Other (Supporting Information)
95MB

Item Type:Article
Title:Who with whom: functional coordination of E2 enzymes by RING E3 ligases during poly-ubiquitylation
Creators Name:Lips, C. and Ritterhoff, T. and Weber, A. and Janowska, M.K. and Mustroph, M. and Sommer, T. and Klevit, R.E.
Abstract:Protein modification with poly-ubiquitin chains is a crucial process involved in a myriad of cellular pathways. Chain synthesis requires two steps: substrate modification with ubiquitin (priming) followed by repetitive ubiquitin-to-ubiquitin attachment (elongation). RING-type E3 ligases catalyze both reactions in collaboration with specific priming and elongating E2 enzymes. We provide kinetic insight into poly-ubiquitylation during protein quality control by showing that priming is the rate-determining step in protein degradation as directed by the yeast ERAD RING E3 ligases, Hrd1 and Doa10. Doa10 cooperates with the dedicated priming E2, Ubc6, while both E3s use Ubc7 for elongation. Here, we provide direct evidence that Hrd1 uses Ubc7 also for priming. We found that Ubc6 has an unusually high basal activity that does not require strong stimulation from an E3. Doa10 exploits this property to pair with Ubc6 over Ubc7 during priming. Our work not only illuminates the mechanisms of specific E2/E3 interplay in ERAD, but also offers a basis to understand how RING E3s may have properties that are tailored to pair with their preferred E2s.
Keywords:E2 Conjugating Enzyme, ER-Associated Protein Degradation, Linchpin, RING E3 Ligase, Ubiquitin
Source:EMBO Journal
ISSN:0261-4189
Publisher:EMBO Press / Wiley
Volume:39
Number:22
Page Range:e104863
Date:16 November 2020
Official Publication:https://doi.org/10.15252/embj.2020104863
PubMed:View item in PubMed

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library