8DAR

Saccharomyces cerevisiae Ufd1/Npl4/Cdc48 complex unbound but in the presence of SUMO-ubiquitin(K48polyUb)-mEOS and ATP

Summary for 8DAR

• Entry DOI: 10.2210/pdb8dar/pdb
• EMDB information: 27273
• Descriptor: Cell division control protein 48, Nuclear protein localization protein 4, Ubiquitin fusion degradation protein 1, ... (6 entities in total)
• Functional Keywords: atpase, atpase complex, ubiquitin, sumo, smt3, quality control, motor protein
• Biological source: Saccharomyces cerevisiae (baker's yeast); More
• Total number of polymer chains: 8
• Total formula weight: 666218.07

Authors

Lee, H.G.,Lima, C.D. (deposition date: 2022-06-14, release date: 2022-11-30, Last modification date: 2024-06-12)

Primary citation

Lee, H.G.,Lemmon, A.A.,Lima, C.D.
SUMO enhances unfolding of SUMO-polyubiquitin-modified substrates by the Ufd1/Npl4/Cdc48 complex.
Proc.Natl.Acad.Sci.USA, 120:e2213703120-e2213703120, 2023

PubMed 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.

PubMed: 36574706
DOI: 10.1073/pnas.2213703120

Experimental method

ELECTRON MICROSCOPY (3 Å)