IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-28425-2.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-28425-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-28425-2?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Onur Dagliyan & Andrey Krokhotin & Irem Ozkan-Dagliyan & Alexander Deiters & Channing J. Der & Klaus M. Hahn & Nikolay V. Dokholyan, 2018. "Computational design of chemogenetic and optogenetic split proteins," Nature Communications, Nature, vol. 9(1), pages 1-8, December.
    2. Alex J. DeGrave & Jeung-Hoi Ha & Stewart N. Loh & Lillian T. Chong, 2018. "Large enhancement of response times of a protein conformational switch by computational design," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
    3. Alfredo Quijano-Rubio & Hsien-Wei Yeh & Jooyoung Park & Hansol Lee & Robert A. Langan & Scott E. Boyken & Marc J. Lajoie & Longxing Cao & Cameron M. Chow & Marcos C. Miranda & Jimin Wi & Hyo Jeong Hon, 2021. "De novo design of modular and tunable protein biosensors," Nature, Nature, vol. 591(7850), pages 482-487, March.
    4. Jordan J Clark & Mark L Benson & Richard D Smith & Heather A Carlson, 2019. "Inherent versus induced protein flexibility: Comparisons within and between apo and holo structures," PLOS Computational Biology, Public Library of Science, vol. 15(1), pages 1-21, January.
    5. Sarah V. Faull & Andy M. C. Lau & Chloe Martens & Zainab Ahdash & Kjetil Hansen & Hugo Yebenes & Carla Schmidt & Fabienne Beuron & Nora B. Cronin & Edward P. Morris & Argyris Politis, 2019. "Structural basis of Cullin 2 RING E3 ligase regulation by the COP9 signalosome," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    6. Zhong Guo & Oleh Smutok & Wayne A. Johnston & Patricia Walden & Jacobus P. J. Ungerer & Thomas S. Peat & Janet Newman & Jake Parker & Tom Nebl & Caryn Hepburn & Artem Melman & Richard J. Suderman & Ev, 2021. "Design of a methotrexate-controlled chemical dimerization system and its use in bio-electronic devices," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    7. Hesam N. Motlagh & James O. Wrabl & Jing Li & Vincent J. Hilser, 2014. "The ensemble nature of allostery," Nature, Nature, vol. 508(7496), pages 331-339, April.
    8. Yan Ni & Bas J. H. M. Rosier & Eva A. Aalen & Eva T. L. Hanckmann & Lieuwe Biewenga & Anna-Maria Makri Pistikou & Bart Timmermans & Chris Vu & Sophie Roos & Remco Arts & Wentao Li & Tom F. A. Greef & , 2021. "A plug-and-play platform of ratiometric bioluminescent sensors for homogeneous immunoassays," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    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.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Zhong Guo & Oleh Smutok & Wayne A. Johnston & Patricia Walden & Jacobus P. J. Ungerer & Thomas S. Peat & Janet Newman & Jake Parker & Tom Nebl & Caryn Hepburn & Artem Melman & Richard J. Suderman & Ev, 2021. "Design of a methotrexate-controlled chemical dimerization system and its use in bio-electronic devices," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    2. Xueyan Chen & Qianqian Ding & Chao Bi & Jian Ruan & Shikuan Yang, 2022. "Lossless enrichment of trace analytes in levitating droplets for multiphase and multiplex detection," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    3. Yashavantha L. Vishweshwaraiah & Jiaxing Chen & Venkat R. Chirasani & Erdem D. Tabdanov & Nikolay V. Dokholyan, 2021. "Two-input protein logic gate for computation in living cells," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    4. Jonathan Schubert & Andrea Schulze & Chrisostomos Prodromou & Hannes Neuweiler, 2021. "Two-colour single-molecule photoinduced electron transfer fluorescence imaging microscopy of chaperone dynamics," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    5. Zhihong Xiao & Jinyin Zha & Xu Yang & Tingting Huang & Shuxin Huang & Qi Liu & Xiaozheng Wang & Jie Zhong & Jianting Zheng & Rubing Liang & Zixin Deng & Jian Zhang & Shuangjun Lin & Shaobo Dai, 2024. "A three-level regulatory mechanism of the aldo-keto reductase subfamily AKR12D," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    6. Yuya Nishida & Sachiko Yanagisawa & Rikuri Morita & Hideki Shigematsu & Kyoko Shinzawa-Itoh & Hitomi Yuki & Satoshi Ogasawara & Ken Shimuta & Takashi Iwamoto & Chisa Nakabayashi & Waka Matsumura & His, 2022. "Identifying antibiotics based on structural differences in the conserved allostery from mitochondrial heme-copper oxidases," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    7. Yasmine S. Zubi & Kosuke Seki & Ying Li & Andrew C. Hunt & Bingqing Liu & Benoît Roux & Michael C. Jewett & Jared C. Lewis, 2022. "Metal-responsive regulation of enzyme catalysis using genetically encoded chemical switches," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    8. David P. Tilly & Jean-Paul Heeb & Simon J. Webb & Jonathan Clayden, 2023. "Switching imidazole reactivity by dynamic control of tautomer state in an allosteric foldamer," Nature Communications, Nature, vol. 14(1), pages 1-7, December.
    9. Huimeng Wang & Yi Fan & Yaqi Hou & Baiyi Chen & Jinmei Lei & Shijie Yu & Xinyu Chen & Xu Hou, 2022. "Host-guest liquid gating mechanism with specific recognition interface behavior for universal quantitative chemical detection," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    10. Luhao Zhang & Maodong Li & Zhirong Liu, 2018. "A comprehensive ensemble model for comparing the allosteric effect of ordered and disordered proteins," PLOS Computational Biology, Public Library of Science, vol. 14(12), pages 1-22, December.
    11. Lauren Gambill & August Staubus & Kim Wai Mo & Andrea Ameruoso & James Chappell, 2023. "A split ribozyme that links detection of a native RNA to orthogonal protein outputs," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    12. William M. Dawson & Kathryn L. Shelley & Jordan M. Fletcher & D. Arne Scott & Lucia Lombardi & Guto G. Rhys & Tania J. LaGambina & Ulrike Obst & Antony J. Burton & Jessica A. Cross & George Davies & F, 2023. "Differential sensing with arrays of de novo designed peptide assemblies," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    13. Manuel Weh & Kazutaka Shoyama & Frank Würthner, 2023. "Preferential molecular recognition of heterochiral guests within a cyclophane receptor," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    14. Stacey E. Chin & Christina Schindler & Lisa Vinall & Roger B. Dodd & Lisa Bamber & Sandrine Legg & Anna Sigurdardottir & D. Gareth Rees & Tim I. M. Malcolm & Samantha J. Spratley & Cecilia Granéli & J, 2023. "A simeprevir-inducible molecular switch for the control of cell and gene therapies," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    15. Robert E. Jefferson & Aurélien Oggier & Andreas Füglistaler & Nicolas Camviel & Mahdi Hijazi & Ana Rico Villarreal & Caroline Arber & Patrick Barth, 2023. "Computational design of dynamic receptor—peptide signaling complexes applied to chemotaxis," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    16. Federica Maschietto & Uriel N. Morzan & Florentina Tofoleanu & Aria Gheeraert & Apala Chaudhuri & Gregory W. Kyro & Peter Nekrasov & Bernard Brooks & J. Patrick Loria & Ivan Rivalta & Victor S. Batist, 2023. "Turning up the heat mimics allosteric signaling in imidazole-glycerol phosphate synthase," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    17. Marko Novinec, 2017. "Computational investigation of conformational variability and allostery in cathepsin K and other related peptidases," PLOS ONE, Public Library of Science, vol. 12(8), pages 1-22, August.
    18. Leonila Lagunes & Lee Bardwell & German A Enciso, 2020. "Effect of magnitude and variability of energy of activation in multisite ultrasensitive biochemical processes," PLOS Computational Biology, Public Library of Science, vol. 16(8), pages 1-26, August.
    19. Yichen Yu & Robert T. O’Neill & Roman Boulatov & Ross A. Widenhoefer & Stephen L. Craig, 2023. "Allosteric control of olefin isomerization kinetics via remote metal binding and its mechanochemical analysis," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    20. Robert Kalescky & Hongyu Zhou & Jin Liu & Peng Tao, 2016. "Rigid Residue Scan Simulations Systematically Reveal Residue Entropic Roles in Protein Allostery," PLOS Computational Biology, Public Library of Science, vol. 12(4), pages 1-21, April.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28425-2. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.