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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