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Design of a water-soluble transmembrane receptor kinase with intact molecular function by QTY code

Author

Listed:
  • Mengke Li

    (Shanghai Jiao Tong University
    Massachusetts Institute of Technology)

  • Hongzhi Tang

    (Shanghai Jiao Tong University)

  • Rui Qing

    (Shanghai Jiao Tong University)

  • Yanze Wang

    (Massachusetts Institute of Technology)

  • Jiongqin Liu

    (Shanghai Jiao Tong University)

  • Rui Wang

    (Shanghai Jiao Tong University)

  • Shan Lyu

    (Shanghai Jiao Tong University)

  • Lina Ma

    (Shanghai Jiao Tong University)

  • Ping Xu

    (Shanghai Jiao Tong University)

  • Shuguang Zhang

    (Massachusetts Institute of Technology)

  • Fei Tao

    (Shanghai Jiao Tong University)

Abstract

Membrane proteins are critical to biological processes and central to life sciences and modern medicine. However, membrane proteins are notoriously challenging to study, mainly owing to difficulties dictated by their highly hydrophobic nature. Previously, we reported QTY code, which is a simple method for designing water-soluble membrane proteins. Here, we apply QTY code to a transmembrane receptor, histidine kinase CpxA, to render it completely water-soluble. The designed CpxAQTY exhibits expected biophysical properties and highly preserved native molecular function, including the activities of (i) autokinase, (ii) phosphotransferase, (iii) phosphatase, and (iv) signaling receptor, involving a water-solubilized transmembrane domain. We probe the principles underlying the balance of structural stability and activity in the water-solubilized transmembrane domain. Computational approaches suggest that an extensive and dynamic hydrogen-bond network introduced by QTY code and its flexibility may play an important role. Our successful functional preservation further substantiates the robustness and comprehensiveness of QTY code.

Suggested Citation

  • Mengke Li & Hongzhi Tang & Rui Qing & Yanze Wang & Jiongqin Liu & Rui Wang & Shan Lyu & Lina Ma & Ping Xu & Shuguang Zhang & Fei Tao, 2024. "Design of a water-soluble transmembrane receptor kinase with intact molecular function by QTY code," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48513-9
    DOI: 10.1038/s41467-024-48513-9
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    References listed on IDEAS

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