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Conserved degronome features governing quality control associated proteolysis

Author

Listed:
  • Bayan Mashahreh

    (The Hebrew University of Jerusalem)

  • Shir Armony

    (The Hebrew University of Jerusalem)

  • Kristoffer Enøe Johansson

    (University of Copenhagen)

  • Alon Chappleboim

    (The Hebrew University of Jerusalem)

  • Nir Friedman

    (The Hebrew University of Jerusalem)

  • Richard G. Gardner

    (University of Washington)

  • Rasmus Hartmann-Petersen

    (University of Copenhagen)

  • Kresten Lindorff-Larsen

    (University of Copenhagen)

  • Tommer Ravid

    (The Hebrew University of Jerusalem)

Abstract

The eukaryotic proteome undergoes constant surveillance by quality control systems that either sequester, refold, or eliminate aberrant proteins by ubiquitin-dependent mechanisms. Ubiquitin-conjugation necessitates the recognition of degradation determinants, termed degrons, by their cognate E3 ubiquitin-protein ligases. To learn about the distinctive properties of quality control degrons, we performed an unbiased peptidome stability screen in yeast. The search identify a large cohort of proteome-derived degrons, some of which exhibited broad E3 ligase specificity. Consequent application of a machine-learning algorithm establishes constraints governing degron potency, including the amino acid composition and secondary structure propensities. According to the set criteria, degrons with transmembrane domain-like characteristics are the most probable sequences to act as degrons. Similar quality control degrons are present in viral and human proteins, suggesting conserved degradation mechanisms. Altogether, the emerging data indicate that transmembrane domain-like degron features have been preserved in evolution as key quality control determinants of protein half-life.

Suggested Citation

  • Bayan Mashahreh & Shir Armony & Kristoffer Enøe Johansson & Alon Chappleboim & Nir Friedman & Richard G. Gardner & Rasmus Hartmann-Petersen & Kresten Lindorff-Larsen & Tommer Ravid, 2022. "Conserved degronome features governing quality control associated proteolysis," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35298-y
    DOI: 10.1038/s41467-022-35298-y
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    Cited by:

    1. Ka-Yiu Edwin Kong & Susmitha Shankar & Frank Rühle & Anton Khmelinskii, 2023. "Orphan quality control by an SCF ubiquitin ligase directed to pervasive C-degrons," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Martin Grønbæk-Thygesen & Vasileios Voutsinos & Kristoffer E. Johansson & Thea K. Schulze & Matteo Cagiada & Line Pedersen & Lene Clausen & Snehal Nariya & Rachel L. Powell & Amelie Stein & Douglas M., 2024. "Deep mutational scanning reveals a correlation between degradation and toxicity of thousands of aspartoacylase variants," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. Lene Clausen & Vasileios Voutsinos & Matteo Cagiada & Kristoffer E. Johansson & Martin Grønbæk-Thygesen & Snehal Nariya & Rachel L. Powell & Magnus K. N. Have & Vibe H. Oestergaard & Amelie Stein & Do, 2024. "A mutational atlas for Parkin proteostasis," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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