1. Microbiology and Infectious Disease
  2. Structural Biology and Molecular Biophysics

Structural basis for diguanylate cyclase activation by its binding partner in Pseudomonas aeruginosa

  1. Gukui Chen
  2. Jiashen Zhou
  3. Yili Zuo
  4. Weiping Huo
  5. Juan Peng
  6. Meng Li
  7. Yani Zhang
  8. Tietao Wang
  9. Lin Zhang
  10. Liang Zhang  Is a corresponding author
  11. Haihua Liang  Is a corresponding author
  1. Northwest University, China
  2. Shanghai Jiao Tong University, China
https://doi.org/10.7554/eLife.67289
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Cite this article
  1. Gukui Chen
  2. Jiashen Zhou
  3. Yili Zuo
  4. Weiping Huo
  5. Juan Peng
  6. Meng Li
  7. Yani Zhang
  8. Tietao Wang
  9. Lin Zhang
  10. Liang Zhang
  11. Haihua Liang
(2021)
Structural basis for diguanylate cyclase activation by its binding partner in Pseudomonas aeruginosa
eLife 10:e67289.
https://doi.org/10.7554/eLife.67289
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  3. Download .RIS

Abstract

Cyclic-di-guanosine monophosphate (c-di-GMP) is an important effector associated with acute-chronic infection transition in Pseudomonas aeruginosa. Previously, we reported a signaling network SiaABCD which regulates biofilm formation by modulating c-di-GMP level. However, the mechanism for SiaD activation by SiaC remains elusive. Here we determine the crystal structure of SiaC-SiaD-GpCpp complex and revealed a unique mirror symmetric conformation: two SiaD form a dimer with long stalk domains, while four SiaC bind to the conserved motifs on the stalks of SiaD and stabilize the conformation for further enzymatic catalysis. Furthermore, SiaD alone exhibits an inactive pentamer conformation in solution, demonstrating that SiaC activates SiaD through a dynamic mechanism of promoting the formation of active SiaD dimers. Mutagenesis assay confirmed that the stalks of SiaD are necessary for its activation. Together, we reveal a novel mechanism for DGC activation, which clarifies the regulatory networks of c-di-GMP signaling.

Data availability

Diffraction data have been deposited in PDB under the accession code 6M3O

Article and author information

Author details

  1. Gukui Chen

    Northwest University, Xi'an, China
    Competing interests
    The authors declare that no competing interests exist.

  2. Jiashen Zhou

    Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.

  3. Yili Zuo

    Northwest University, Xi'an, China
    Competing interests
    The authors declare that no competing interests exist.

  4. Weiping Huo

    Northwest University, Xi'an, China
    Competing interests
    The authors declare that no competing interests exist.

  5. Juan Peng

    Northwest University, Xi'an, China
    Competing interests
    The authors declare that no competing interests exist.

  6. Meng Li

    Northwest University, Xi'an, China
    Competing interests
    The authors declare that no competing interests exist.

  7. Yani Zhang

    Northwest University, Xi'an, China
    Competing interests
    The authors declare that no competing interests exist.

  8. Tietao Wang

    Northwest University, Xi'an, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8540-436X

  9. Lin Zhang

    Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Shanghai Jiao Tong University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.

  10. Liang Zhang

    Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University, Shanghai, China
    For correspondence
    liangzhang2014@sjtu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.

  11. Haihua Liang

    Northwest University, Xi'an, China
    For correspondence
    lianghh@nwu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9639-1867

Funding

National Natural Science Foundation of China (31700064)

  • Gukui Chen

National Natural Science Foundation of China (21722802)

  • Liang Zhang

National Natural Science Foundation of China (91853118)

  • Liang Zhang

National Natural Science Foundation of China (32170188)

  • Haihua Liang

National Natural Science Foundation of China (31870060)

  • Haihua Liang

Natural Science Basic Research Program of Shaanxi Province (2019JQ-134)

  • Gukui Chen

National Natural Science Foundation of China (32170178)

  • Gukui Chen

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2021, Chen et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Gukui Chen
  2. Jiashen Zhou
  3. Yili Zuo
  4. Weiping Huo
  5. Juan Peng
  6. Meng Li
  7. Yani Zhang
  8. Tietao Wang
  9. Lin Zhang
  10. Liang Zhang
  11. Haihua Liang
(2021)
Structural basis for diguanylate cyclase activation by its binding partner in Pseudomonas aeruginosa
eLife 10:e67289.
https://doi.org/10.7554/eLife.67289

Share this article

https://doi.org/10.7554/eLife.67289

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