Structural basis for diguanylate cyclase activation by its binding partner in Pseudomonas aeruginosa
- Northwest University, China
- Shanghai Jiao Tong University, China
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
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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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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