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Single-molecule analysis of specificity and multivalency in binding of short linear substrate motifs to the APC/C

Author

Listed:
  • Nairi Hartooni

    (University of California
    University of California)

  • Jongmin Sung

    (University of California
    University of California
    Roche Sequencing Solutions)

  • Ankur Jain

    (University of California
    University of California
    Whitehead Institute for Biomedical Research)

  • David O. Morgan

    (University of California
    University of California)

Abstract

Robust regulatory signals in the cell often depend on interactions between short linear motifs (SLiMs) and globular proteins. Many of these interactions are poorly characterized because the binding proteins cannot be produced in the amounts needed for traditional methods. To address this problem, we developed a single-molecule off-rate (SMOR) assay based on microscopy of fluorescent ligand binding to immobilized protein partners. We used it to characterize substrate binding to the Anaphase-Promoting Complex/Cyclosome (APC/C), a ubiquitin ligase that triggers chromosome segregation. We find that SLiMs in APC/C substrates (the D box and KEN box) display distinct affinities and specificities for the substrate-binding subunits of the APC/C, and we show that multiple SLiMs in a substrate generate a high-affinity multivalent interaction. The remarkably adaptable substrate-binding mechanisms of the APC/C have the potential to govern the order of substrate destruction in mitosis.

Suggested Citation

  • Nairi Hartooni & Jongmin Sung & Ankur Jain & David O. Morgan, 2022. "Single-molecule analysis of specificity and multivalency in binding of short linear substrate motifs to the APC/C," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28031-2
    DOI: 10.1038/s41467-022-28031-2
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    References listed on IDEAS

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    1. Leifu Chang & Ziguo Zhang & Jing Yang & Stephen H. McLaughlin & David Barford, 2014. "Molecular architecture and mechanism of the anaphase-promoting complex," Nature, Nature, vol. 513(7518), pages 388-393, September.
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