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Engineering and exploiting synthetic allostery of NanoLuc luciferase

Author

Listed:
  • Zhong Guo

    (ARC Centre of Excellence in Synthetic Biology
    Queensland University of Technology
    Queensland University of Technology)

  • Rinky D. Parakra

    (University of Exeter)

  • Ying Xiong

    (University of Virginia)

  • Wayne A. Johnston

    (ARC Centre of Excellence in Synthetic Biology
    Queensland University of Technology
    Queensland University of Technology)

  • Patricia Walden

    (ARC Centre of Excellence in Synthetic Biology
    Queensland University of Technology
    Queensland University of Technology)

  • Selvakumar Edwardraja

    (The University of Queensland)

  • Shayli Varasteh Moradi

    (ARC Centre of Excellence in Synthetic Biology
    Queensland University of Technology
    Queensland University of Technology)

  • Jacobus P. J. Ungerer

    (Pathology Queensland
    University of Queensland)

  • Hui-wang Ai

    (University of Virginia)

  • Jonathan J. Phillips

    (University of Exeter
    Alan Turing Institute)

  • Kirill Alexandrov

    (ARC Centre of Excellence in Synthetic Biology
    Queensland University of Technology
    Queensland University of Technology
    Queensland University of Technology)

Abstract

Allostery enables proteins to interconvert different biochemical signals and form complex metabolic and signaling networks. We hypothesize that circular permutation of proteins increases the probability of functional coupling of new N- and C- termini with the protein’s active center through increased local structural disorder. To test this we construct a synthetically allosteric version of circular permutated NanoLuc luciferase that can be activated through ligand-induced intramolecular non-covalent cyclisation. This switch module is tolerant of the structure of binding domains and their ligands, and can be used to create biosensors of proteins and small molecules. The developed biosensors covers a range of emission wavelengths and displays sensitivity as low as 50pM and dynamic range as high as 16-fold and could quantify their cognate ligand in human fluids. We apply hydrogen exchange kinetic mass spectroscopy to analyze time resolved structural changes in the developed biosensors and observe ligand-mediated folding of newly created termini.

Suggested Citation

  • Zhong Guo & Rinky D. Parakra & Ying Xiong & Wayne A. Johnston & Patricia Walden & Selvakumar Edwardraja & Shayli Varasteh Moradi & Jacobus P. J. Ungerer & Hui-wang Ai & Jonathan J. Phillips & Kirill A, 2022. "Engineering and exploiting synthetic allostery of NanoLuc luciferase," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28425-2
    DOI: 10.1038/s41467-022-28425-2
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    References listed on IDEAS

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    Cited by:

    1. Michal Nemergut & Daniel Pluskal & Jana Horackova & Tereza Sustrova & Jan Tulis & Tomas Barta & Racha Baatallah & Glwadys Gagnot & Veronika Novakova & Marika Majerova & Karolina Sedlackova & Sérgio M., 2023. "Illuminating the mechanism and allosteric behavior of NanoLuc luciferase," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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