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Disentangling the recognition complexity of a protein hub using a nanopore

Author

Listed:
  • Lauren Ashley Mayse

    (Syracuse University
    Syracuse University)

  • Ali Imran

    (Syracuse University)

  • Motahareh Ghahari Larimi

    (Syracuse University
    National Institutes of Health)

  • Michael S. Cosgrove

    (State University of New York - Upstate Medical University, 4249 Weiskotten Hall)

  • Aaron James Wolfe

    (Syracuse University
    Ichor Life Sciences, Inc
    Clarkson University
    State University of New York, College of Environmental Science and Forestry)

  • Liviu Movileanu

    (Syracuse University
    Syracuse University
    Syracuse University)

Abstract

WD40 repeat proteins are frequently involved in processing cell signaling and scaffolding large multi-subunit machineries. Despite their significance in physiological and disease-like conditions, their reversible interactions with other proteins remain modestly examined. Here, we show the development and validation of a protein nanopore for the detection and quantification of WD40 repeat protein 5 (WDR5), a chromatin-associated hub involved in epigenetic regulation of histone methylation. Our nanopore sensor is equipped with a 14-residue Win motif of mixed lineage leukemia 4 methyltransferase (MLL4Win), a WDR5 ligand. Our approach reveals a broad dynamic range of MLL4Win-WDR5 interactions and three distant subpopulations of binding events, representing three modes of protein recognition. The three binding events are confirmed as specific interactions using a weakly binding WDR5 derivative and various environmental contexts. These outcomes demonstrate the substantial sensitivity of our nanopore sensor, which can be utilized in protein analytics.

Suggested Citation

  • Lauren Ashley Mayse & Ali Imran & Motahareh Ghahari Larimi & Michael S. Cosgrove & Aaron James Wolfe & Liviu Movileanu, 2022. "Disentangling the recognition complexity of a protein hub using a nanopore," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28465-8
    DOI: 10.1038/s41467-022-28465-8
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    References listed on IDEAS

    as
    1. Fabian Paul & Christoph Wehmeyer & Esam T. Abualrous & Hao Wu & Michael D. Crabtree & Johannes Schöneberg & Jane Clarke & Christian Freund & Thomas R. Weikl & Frank Noé, 2017. "Protein-peptide association kinetics beyond the seconds timescale from atomistic simulations," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
    2. Nicole Stéphanie Galenkamp & Misha Soskine & Jos Hermans & Carsten Wloka & Giovanni Maglia, 2018. "Direct electrical quantification of glucose and asparagine from bodily fluids using nanopores," Nature Communications, Nature, vol. 9(1), pages 1-8, December.
    3. Justin M. Di Trani & Stephane De Cesco & Rebecca O’Leary & Jessica Plescia & Claudia Jorge Nascimento & Nicolas Moitessier & Anthony K. Mittermaier, 2018. "Rapid measurement of inhibitor binding kinetics by isothermal titration calorimetry," Nature Communications, Nature, vol. 9(1), pages 1-7, December.
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    Cited by:

    1. Mohammad Ahmad & Jeung-Hoi Ha & Lauren A. Mayse & Maria F. Presti & Aaron J. Wolfe & Kelsey J. Moody & Stewart N. Loh & Liviu Movileanu, 2023. "A generalizable nanopore sensor for highly specific protein detection at single-molecule precision," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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