SUMO enhances unfolding of SUMO-polyubiquitin-modified substrates by the Ufd1/Npl4/Cdc48 complex Journal Article


Authors: Lee, H. G.; Lemmon, A. A.; Lima, C. D.
Article Title: SUMO enhances unfolding of SUMO-polyubiquitin-modified substrates by the Ufd1/Npl4/Cdc48 complex
Abstract: The Ufd1/Npl4/Cdc48 complex is a universal protein segregase that plays key roles in eukaryotic cellular processes. Its functions orchestrating the clearance or removal of polyubiquitylated targets are established; however, prior studies suggest that the complex also targets substrates modified by the ubiquitin-like protein SUMO. Here, we show that interactions between Ufd1 and SUMO enhance unfolding of substrates modified by SUMO-polyubiquitin hybrid chains by the budding yeast Ufd1/Npl4/ Cdc48 complex compared to substrates modified by polyubiquitin chains, a difference that is accentuated when the complex has a choice between these substrates. Incubating Ufd1/Npl4/Cdc48 with a substrate modified by a SUMO-polyubiquitin hybrid chain produced a series of single-particle cryo-EM structures that reveal features of interactions between Ufd1/Npl4/Cdc48 and ubiquitin prior to and during unfolding of ubiquitin. These results are consistent with cellular functions for SUMO and ubiquitin modifications and support a physical model wherein Ufd1/Npl4/Cdc48, SUMO, and ubiquitin conjugation pathways converge to promote clearance of proteins modified with SUMO and polyubiquitin. © 2022 the Author(s).
Keywords: genetics; ubiquitin; quality control; cell cycle protein; metabolism; cell cycle proteins; endoplasmic reticulum; stress; saccharomyces cerevisiae proteins; saccharomyces cerevisiae protein; polyubiquitin; sumo; valosin containing protein; segregase
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 120
Issue: 1
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2023-01-03
Start Page: e2213703120
Language: English
DOI: 10.1073/pnas.2213703120
PUBMED: 36574706
PROVIDER: scopus
PMCID: PMC9910466
DOI/URL:
Notes: Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Christopher Lima -- Export Date: 1 February 2023 -- Source: Scopus
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MSK Authors
  1. Christopher D Lima
    103 Lima
  2. Hye in Lee
    1 Lee
  3. Abigail Alix Lemmon
    2 Lemmon