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Updated: Jun 14, 2025

Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay
13:10

Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay

Published on: June 9, 2017

10.0K

Genesis and regulation of C-terminal cyclic imides from protein damage

Wenqing Xu, Zhenguang Zhao, Matthew Su

    Biorxiv : the Preprint Server for Biology
    |August 30, 2024
    PubMed

    Insights

    C-terminal cyclic imides are protein damage events recognized by cereblon (CRBN). This study identifies factors influencing their formation and impact on protein stability.

    Area of Science:

    • Biochemistry
    • Molecular Biology
    • Proteomics

    Background:

    • C-terminal cyclic imides are post-translational modifications (PTMs) resulting from spontaneous cleavage of asparagine/glutamine residues.
    • These modifications represent irreversible protein damage and are recognized by the E3 ligase substrate adapter cereblon (CRBN).
    • Cellular quality control mechanisms, including CRBN, are crucial for preventing deleterious effects of these aging-related modifications.

    Purpose of the Study:

    • To characterize structural determinants of protein susceptibility to C-terminal cyclic imide formation.
    • To compare C-terminal cyclic imide formation with deamidation.
    • To investigate the impact of extrinsic factors and protein aggregation on C-terminal cyclic imide formation.

    Main Methods:

    • Peptide and protein structural analysis.
    • Comparison of C-terminal cyclic imide formation versus deamidation.
    • Investigation of extrinsic factors (solution properties, stressors) on protein modification.

    Main Results:

    • Identified primary and secondary structures that promote intrinsic C-terminal cyclic imide formation.
    • Demonstrated that extrinsic factors can promote C-terminal cyclic imide formation in susceptible proteins like glutathione synthetase (GSS).
    • Showed that CRBN removes protein damage products, preventing aggregation.

    Conclusions:

    • Provided insights into proteome regions prone to C-terminal cyclic imide modifications.
    • Elucidated the effects of this protein damage on protein stability.
    • Highlighted the biological role of CRBN in managing C-terminal cyclic imide damage.

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