Cryo-EM structures of Gid12-bound GID E3 reveal steric blockade as a mechanism inhibiting substrate ubiquitylation

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Cryo-EM structures of Gid12-bound GID E3 reveal steric blockade as a mechanism inhibiting substrate ubiquitylation. / Qiao, Shuai; Lee, Chia-Wei; Sherpa, Dawafuti; Chrustowicz, Jakub; Cheng, Jingdong; Duennebacke, Maximilian; Steigenberger, Barbara; Karayel, Ozge; Vu, Duc Tung; von Gronau, Susanne; Mann, Matthias; Wilfling, Florian; Schulman, Brenda A.

In: Nature Communications, Vol. 13, 3041, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Qiao, S, Lee, C-W, Sherpa, D, Chrustowicz, J, Cheng, J, Duennebacke, M, Steigenberger, B, Karayel, O, Vu, DT, von Gronau, S, Mann, M, Wilfling, F & Schulman, BA 2022, 'Cryo-EM structures of Gid12-bound GID E3 reveal steric blockade as a mechanism inhibiting substrate ubiquitylation', Nature Communications, vol. 13, 3041. https://doi.org/10.1038/s41467-022-30803-9

APA

Qiao, S., Lee, C-W., Sherpa, D., Chrustowicz, J., Cheng, J., Duennebacke, M., Steigenberger, B., Karayel, O., Vu, D. T., von Gronau, S., Mann, M., Wilfling, F., & Schulman, B. A. (2022). Cryo-EM structures of Gid12-bound GID E3 reveal steric blockade as a mechanism inhibiting substrate ubiquitylation. Nature Communications, 13, [3041]. https://doi.org/10.1038/s41467-022-30803-9

Vancouver

Qiao S, Lee C-W, Sherpa D, Chrustowicz J, Cheng J, Duennebacke M et al. Cryo-EM structures of Gid12-bound GID E3 reveal steric blockade as a mechanism inhibiting substrate ubiquitylation. Nature Communications. 2022;13. 3041. https://doi.org/10.1038/s41467-022-30803-9

Author

Qiao, Shuai ; Lee, Chia-Wei ; Sherpa, Dawafuti ; Chrustowicz, Jakub ; Cheng, Jingdong ; Duennebacke, Maximilian ; Steigenberger, Barbara ; Karayel, Ozge ; Vu, Duc Tung ; von Gronau, Susanne ; Mann, Matthias ; Wilfling, Florian ; Schulman, Brenda A. / Cryo-EM structures of Gid12-bound GID E3 reveal steric blockade as a mechanism inhibiting substrate ubiquitylation. In: Nature Communications. 2022 ; Vol. 13.

Bibtex

@article{17144d612595445d821c9ee4854d0d36,
title = "Cryo-EM structures of Gid12-bound GID E3 reveal steric blockade as a mechanism inhibiting substrate ubiquitylation",
abstract = "Protein degradation, a major eukaryotic response to cellular signals, is subject to numerous layers of regulation. In yeast, the evolutionarily conserved GID E3 ligase mediates glucose-induced degradation of fructose-1,6-bisphosphatase (Fbp1), malate dehydrogenase (Mdh2), and other gluconeogenic enzymes. {"}GID{"} is a collection of E3 ligase complexes; a core scaffold, RING-type catalytic core, and a supramolecular assembly module together with interchangeable substrate receptors select targets for ubiquitylation. However, knowledge of additional cellular factors directly regulating GID-type E3s remains rudimentary. Here, we structurally and biochemically characterize Gid12 as a modulator of the GID E3 ligase complex. Our collection of cryo-EM reconstructions shows that Gid12 forms an extensive interface sealing the substrate receptor Gid4 onto the scaffold, and remodeling the degron binding site. Gid12 also sterically blocks a recruited Fbp1 or Mdh2 from the ubiquitylation active sites. Our analysis of the role of Gid12 establishes principles that may more generally underlie E3 ligase regulation.",
keywords = "Cryoelectron Microscopy, Gluconeogenesis/physiology, Saccharomyces cerevisiae/metabolism, Saccharomyces cerevisiae Proteins/metabolism, Ubiquitin-Protein Ligases/metabolism, Ubiquitination",
author = "Shuai Qiao and Chia-Wei Lee and Dawafuti Sherpa and Jakub Chrustowicz and Jingdong Cheng and Maximilian Duennebacke and Barbara Steigenberger and Ozge Karayel and Vu, {Duc Tung} and {von Gronau}, Susanne and Matthias Mann and Florian Wilfling and Schulman, {Brenda A}",
note = "{\textcopyright} 2022. The Author(s).",
year = "2022",
doi = "10.1038/s41467-022-30803-9",
language = "English",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Cryo-EM structures of Gid12-bound GID E3 reveal steric blockade as a mechanism inhibiting substrate ubiquitylation

AU - Qiao, Shuai

AU - Lee, Chia-Wei

AU - Sherpa, Dawafuti

AU - Chrustowicz, Jakub

AU - Cheng, Jingdong

AU - Duennebacke, Maximilian

AU - Steigenberger, Barbara

AU - Karayel, Ozge

AU - Vu, Duc Tung

AU - von Gronau, Susanne

AU - Mann, Matthias

AU - Wilfling, Florian

AU - Schulman, Brenda A

N1 - © 2022. The Author(s).

PY - 2022

Y1 - 2022

N2 - Protein degradation, a major eukaryotic response to cellular signals, is subject to numerous layers of regulation. In yeast, the evolutionarily conserved GID E3 ligase mediates glucose-induced degradation of fructose-1,6-bisphosphatase (Fbp1), malate dehydrogenase (Mdh2), and other gluconeogenic enzymes. "GID" is a collection of E3 ligase complexes; a core scaffold, RING-type catalytic core, and a supramolecular assembly module together with interchangeable substrate receptors select targets for ubiquitylation. However, knowledge of additional cellular factors directly regulating GID-type E3s remains rudimentary. Here, we structurally and biochemically characterize Gid12 as a modulator of the GID E3 ligase complex. Our collection of cryo-EM reconstructions shows that Gid12 forms an extensive interface sealing the substrate receptor Gid4 onto the scaffold, and remodeling the degron binding site. Gid12 also sterically blocks a recruited Fbp1 or Mdh2 from the ubiquitylation active sites. Our analysis of the role of Gid12 establishes principles that may more generally underlie E3 ligase regulation.

AB - Protein degradation, a major eukaryotic response to cellular signals, is subject to numerous layers of regulation. In yeast, the evolutionarily conserved GID E3 ligase mediates glucose-induced degradation of fructose-1,6-bisphosphatase (Fbp1), malate dehydrogenase (Mdh2), and other gluconeogenic enzymes. "GID" is a collection of E3 ligase complexes; a core scaffold, RING-type catalytic core, and a supramolecular assembly module together with interchangeable substrate receptors select targets for ubiquitylation. However, knowledge of additional cellular factors directly regulating GID-type E3s remains rudimentary. Here, we structurally and biochemically characterize Gid12 as a modulator of the GID E3 ligase complex. Our collection of cryo-EM reconstructions shows that Gid12 forms an extensive interface sealing the substrate receptor Gid4 onto the scaffold, and remodeling the degron binding site. Gid12 also sterically blocks a recruited Fbp1 or Mdh2 from the ubiquitylation active sites. Our analysis of the role of Gid12 establishes principles that may more generally underlie E3 ligase regulation.

KW - Cryoelectron Microscopy

KW - Gluconeogenesis/physiology

KW - Saccharomyces cerevisiae/metabolism

KW - Saccharomyces cerevisiae Proteins/metabolism

KW - Ubiquitin-Protein Ligases/metabolism

KW - Ubiquitination

U2 - 10.1038/s41467-022-30803-9

DO - 10.1038/s41467-022-30803-9

M3 - Journal article

C2 - 35650207

VL - 13

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 3041

ER -

ID: 331591459