EMD-27278

Single-particle
3.6 Å
EMD-27278 Deposition: 14/06/2022
Map released: 30/11/2022
Last modified: 06/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-27278

Saccharomyces cerevisiae Ufd1/Npl4/Cdc48 complex bound to three ubiquitin moieties and one unfolded ubiquitin in presence of SUMO-ubiquitin(K48polyUb)-mEOS and ATP, state 2 (uD)

EMD-27278

Single-particle
3.6 Å
EMD-27278 Deposition: 14/06/2022
Map released: 30/11/2022
Last modified: 06/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Saccharomyces cerevisiae
Sample: Saccharomyces cerevisiae Ufd1/Npl4/Cdc48 complex bound to three ubiquitin moieties and one unfolded ubiquitin in presence of SUMO-ubiquitin(K48polyUb)-mEOS and ATP, state 2 (uD)
Fitted models: 8daw (Avg. Q-score: 0.378)

Deposition Authors: Lee HG, Lima CD
SUMO enhances unfolding of SUMO-polyubiquitin-modified substrates by the Ufd1/Npl4/Cdc48 complex.
Lee HG, Lemmon AA , Lima CD
(2023) PNAS , 120 , e2213703120 - e2213703120
PUBMED: 36574706
DOI: doi:10.1073/pnas.2213703120
ISSN: 1091-6490
ASTM: PNASA6
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.