Artificial allosteric protein switches with machine-learning-designed receptors
F nuclear magnetic resonance analyses suggest that ligand binding reduces the conformation entropy of the system, increasing the catalytic activity of the reporter domain. The potential practical utility of this approach is demonstrated by engineering Escherichia coli cells with steroid-dependent antibiotic resistance and by developing bioelectronic devices capable of quantifying steroid hormones.
Authors
- Alfredo Quijano‐Rubio (ORCID: https://orcid.org/0000-0003-1567-9530)
- Cagla Ergun Ayva (ORCID: https://orcid.org/0000-0003-2995-1777)
- Gottfried Otting (ORCID: https://orcid.org/0000-0002-0563-0146)
- Zhenling Cui (ORCID: https://orcid.org/0000-0002-5664-8303)
- Maria Micaela Fiorito (ORCID: https://orcid.org/0000-0002-8054-0060)
- Andrew C. Warden (ORCID: https://orcid.org/0000-0003-2683-9798)
- Oliver B. Smith (ORCID: https://orcid.org/0009-0005-6774-5837)
- Colin J. Jackson (ORCID: https://orcid.org/0000-0001-6150-3822)
- Haocheng Qianzhu (ORCID: https://orcid.org/0000-0002-7546-4411)
- Thomas Huber (ORCID: https://orcid.org/0000-0003-2952-4273)
- Kirill A. Alexandrov (ORCID: https://orcid.org/0000-0002-0957-6511)
- Evgeny Katz (ORCID: https://orcid.org/0000-0002-1618-4620)
- Jonathan J. Phillips (ORCID: https://orcid.org/0000-0002-5361-9582)
- Oleh V. Smutok (ORCID: https://orcid.org/0000-0002-9967-3445)
- Gyu Rie Lee (ORCID: https://orcid.org/0000-0002-9119-5303)
- Roxane Mutschler (ORCID: https://orcid.org/0009-0009-2376-4293)
- Kejia Wu (ORCID: https://orcid.org/0000-0002-4532-4290)
- David Baker
- Zhong Guo (ORCID: https://orcid.org/0000-0003-0285-5021)
- Monika Kish
Institutions
- Australian National University (AU)
- Commonwealth Scientific and Industrial Research Organisation (AU)
- Howard Hughes Medical Institute (US)
- Korea Advanced Institute of Science and Technology (KR)
- Queensland University of Technology (AU)
- Clarkson University (US)
- University of Washington (US)
- University of Exeter (GB)
- Cancer Research And Biostatistics (US)
- ARC Centre of Excellence in Synthetic Biology (AU)
- ARC Centre of Excellence for Innovations in Peptide and Protein Science (AU)
Publication Details
- Journal
- Nature Biotechnology
- Published
- 2026-04-15
- DOI
- https://doi.org/10.1038/s41587-026-03081-9
- Primary Topic
- Metalloenzymes and iron-sulfur proteins
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Science Foundation
- Howard Hughes Medical Institute
- Open Philanthropy Project
- Commonwealth Scientific and Industrial Research Organisation
- Medical Research Council
- Australian Research Council
- National Health and Medical Research Council
- Division of Chemical, Bioengineering, Environmental, and Transport Systems