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Journal Article

Multifaceted N-Degron Recognition and Ubiquitylation by GID/CTLH E3 Ligases

MPS-Authors
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Chrustowicz,  Jakub
Schulman, Brenda / Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Max Planck Society;

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Sherpa,  Dawafuti
Schulman, Brenda / Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Max Planck Society;

Loke,  Mun Siong
Schulman, Brenda / Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons131140

Prabu,  J. Rajan
Schulman, Brenda / Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons213292

Schulman,  Brenda
Schulman, Brenda / Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Max Planck Society;

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1-s2.0-S0022283621005842-main.pdf
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1-s2.0-S0022283621005842-mmc1.pdf
(Supplementary material), 12MB

Citation

Chrustowicz, J., Sherpa, D., Teyra, J., Loke, M. S., Popowicz, G. M., Basquin, J., et al. (2022). Multifaceted N-Degron Recognition and Ubiquitylation by GID/CTLH E3 Ligases. Journal of Molecular Biology, 434(2): 167347. doi:10.1016/j.jmb.2021.167347.


Cite as: https://hdl.handle.net/21.11116/0000-0009-C12B-D
Abstract
N-degron E3 ubiquitin ligases recognize specific residues at the N-termini of substrates. Although molecular details of N-degron recognition are known for several E3 ligases, the range of N-terminal motifs that can bind a given E3 substrate binding domain remains unclear. Here, we discovered capacity of Gid4 and Gid10 substrate receptor subunits of yeast "GID"/human "CTLH" multiprotein E3 ligases to tightly bind a wide range of N-terminal residues whose recognition is determined in part by the downstream sequence context. Screening of phage displaying peptide libraries with exposed N-termini identified novel consensus motifs with non-Pro N-terminal residues binding Gid4 or Gid10 with high affinity. Structural data reveal that conformations of flexible loops in Gid4 and Gid10 complement sequences and folds of interacting peptides. Together with analysis of endogenous substrate degrons, the data show that degron identity, substrate domains harboring targeted lysines, and varying E3 ligase higher-order assemblies combinatorially determine efficiency of ubiquitylation and degradation. (c) 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).