GID E3 ligase supramolecular chelate assembly configures multipronged ubiquitin targeting of an oligomeric metabolic enzyme

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

Standard

GID E3 ligase supramolecular chelate assembly configures multipronged ubiquitin targeting of an oligomeric metabolic enzyme. / Sherpa, Dawafuti; Chrustowicz, Jakub; Qiao, Shuai; Langlois, Christine R; Hehl, Laura A; Gottemukkala, Karthik Varma; Hansen, Fynn M; Karayel, Ozge; von Gronau, Susanne; Prabu, J Rajan; Mann, Matthias; Alpi, Arno F; Schulman, Brenda A.

In: Molecular Cell, 22.04.2021.

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

Harvard

Sherpa, D, Chrustowicz, J, Qiao, S, Langlois, CR, Hehl, LA, Gottemukkala, KV, Hansen, FM, Karayel, O, von Gronau, S, Prabu, JR, Mann, M, Alpi, AF & Schulman, BA 2021, 'GID E3 ligase supramolecular chelate assembly configures multipronged ubiquitin targeting of an oligomeric metabolic enzyme', Molecular Cell. https://doi.org/10.1016/j.molcel.2021.03.025

APA

Sherpa, D., Chrustowicz, J., Qiao, S., Langlois, C. R., Hehl, L. A., Gottemukkala, K. V., Hansen, F. M., Karayel, O., von Gronau, S., Prabu, J. R., Mann, M., Alpi, A. F., & Schulman, B. A. (2021). GID E3 ligase supramolecular chelate assembly configures multipronged ubiquitin targeting of an oligomeric metabolic enzyme. Molecular Cell. https://doi.org/10.1016/j.molcel.2021.03.025

Vancouver

Sherpa D, Chrustowicz J, Qiao S, Langlois CR, Hehl LA, Gottemukkala KV et al. GID E3 ligase supramolecular chelate assembly configures multipronged ubiquitin targeting of an oligomeric metabolic enzyme. Molecular Cell. 2021 Apr 22. https://doi.org/10.1016/j.molcel.2021.03.025

Author

Sherpa, Dawafuti ; Chrustowicz, Jakub ; Qiao, Shuai ; Langlois, Christine R ; Hehl, Laura A ; Gottemukkala, Karthik Varma ; Hansen, Fynn M ; Karayel, Ozge ; von Gronau, Susanne ; Prabu, J Rajan ; Mann, Matthias ; Alpi, Arno F ; Schulman, Brenda A. / GID E3 ligase supramolecular chelate assembly configures multipronged ubiquitin targeting of an oligomeric metabolic enzyme. In: Molecular Cell. 2021.

Bibtex

@article{768a1df710a44f35835f12eff265ef2a,
title = "GID E3 ligase supramolecular chelate assembly configures multipronged ubiquitin targeting of an oligomeric metabolic enzyme",
abstract = "How are E3 ubiquitin ligases configured to match substrate quaternary structures? Here, by studying the yeast GID complex (mutation of which causes deficiency in glucose-induced degradation of gluconeogenic enzymes), we discover supramolecular chelate assembly as an E3 ligase strategy for targeting an oligomeric substrate. Cryoelectron microscopy (cryo-EM) structures show that, to bind the tetrameric substrate fructose-1,6-bisphosphatase (Fbp1), two minimally functional GID E3s assemble into the 20-protein Chelator-GIDSR4, which resembles an organometallic supramolecular chelate. The Chelator-GIDSR4 assembly avidly binds multiple Fbp1 degrons so that multiple Fbp1 protomers are simultaneously ubiquitylated at lysines near the allosteric and substrate binding sites. Importantly, key structural and biochemical features, including capacity for supramolecular assembly, are preserved in the human ortholog, the CTLH E3. Based on our integrative structural, biochemical, and cell biological data, we propose that higher-order E3 ligase assembly generally enables multipronged targeting, capable of simultaneously incapacitating multiple protomers and functionalities of oligomeric substrates.",
author = "Dawafuti Sherpa and Jakub Chrustowicz and Shuai Qiao and Langlois, {Christine R} and Hehl, {Laura A} and Gottemukkala, {Karthik Varma} and Hansen, {Fynn M} and Ozge Karayel and {von Gronau}, Susanne and Prabu, {J Rajan} and Matthias Mann and Alpi, {Arno F} and Schulman, {Brenda A}",
note = "Copyright {\textcopyright} 2021 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2021",
month = apr,
day = "22",
doi = "10.1016/j.molcel.2021.03.025",
language = "English",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",

}

RIS

TY - JOUR

T1 - GID E3 ligase supramolecular chelate assembly configures multipronged ubiquitin targeting of an oligomeric metabolic enzyme

AU - Sherpa, Dawafuti

AU - Chrustowicz, Jakub

AU - Qiao, Shuai

AU - Langlois, Christine R

AU - Hehl, Laura A

AU - Gottemukkala, Karthik Varma

AU - Hansen, Fynn M

AU - Karayel, Ozge

AU - von Gronau, Susanne

AU - Prabu, J Rajan

AU - Mann, Matthias

AU - Alpi, Arno F

AU - Schulman, Brenda A

N1 - Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2021/4/22

Y1 - 2021/4/22

N2 - How are E3 ubiquitin ligases configured to match substrate quaternary structures? Here, by studying the yeast GID complex (mutation of which causes deficiency in glucose-induced degradation of gluconeogenic enzymes), we discover supramolecular chelate assembly as an E3 ligase strategy for targeting an oligomeric substrate. Cryoelectron microscopy (cryo-EM) structures show that, to bind the tetrameric substrate fructose-1,6-bisphosphatase (Fbp1), two minimally functional GID E3s assemble into the 20-protein Chelator-GIDSR4, which resembles an organometallic supramolecular chelate. The Chelator-GIDSR4 assembly avidly binds multiple Fbp1 degrons so that multiple Fbp1 protomers are simultaneously ubiquitylated at lysines near the allosteric and substrate binding sites. Importantly, key structural and biochemical features, including capacity for supramolecular assembly, are preserved in the human ortholog, the CTLH E3. Based on our integrative structural, biochemical, and cell biological data, we propose that higher-order E3 ligase assembly generally enables multipronged targeting, capable of simultaneously incapacitating multiple protomers and functionalities of oligomeric substrates.

AB - How are E3 ubiquitin ligases configured to match substrate quaternary structures? Here, by studying the yeast GID complex (mutation of which causes deficiency in glucose-induced degradation of gluconeogenic enzymes), we discover supramolecular chelate assembly as an E3 ligase strategy for targeting an oligomeric substrate. Cryoelectron microscopy (cryo-EM) structures show that, to bind the tetrameric substrate fructose-1,6-bisphosphatase (Fbp1), two minimally functional GID E3s assemble into the 20-protein Chelator-GIDSR4, which resembles an organometallic supramolecular chelate. The Chelator-GIDSR4 assembly avidly binds multiple Fbp1 degrons so that multiple Fbp1 protomers are simultaneously ubiquitylated at lysines near the allosteric and substrate binding sites. Importantly, key structural and biochemical features, including capacity for supramolecular assembly, are preserved in the human ortholog, the CTLH E3. Based on our integrative structural, biochemical, and cell biological data, we propose that higher-order E3 ligase assembly generally enables multipronged targeting, capable of simultaneously incapacitating multiple protomers and functionalities of oligomeric substrates.

U2 - 10.1016/j.molcel.2021.03.025

DO - 10.1016/j.molcel.2021.03.025

M3 - Journal article

C2 - 33905682

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

ER -

ID: 261518068