8WCN

Cryo-EM structure of PAO1-ImcA with GMPCPP

Summary for 8WCN

• Entry DOI: 10.2210/pdb8wcn/pdb
• EMDB information: 37444
• Descriptor: Diguanylate cyclase, PHOSPHOMETHYLPHOSPHONIC ACID GUANYLATE ESTER, MAGNESIUM ION (3 entities in total)
• Functional Keywords: ggdef domain, diguanylate cyclase activity, membrane protein
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 2
• Total formula weight: 104793.05

Authors

Zhan, X.L.,Zhang, K.,Wang, C.C.,Fan, Q.,Tang, X.J.,Zhang, X.,Wang, K.,Fu, Y.,Liang, H.H. (deposition date: 2023-09-13, release date: 2024-03-13)

Primary citation

Zhan, X.,Zhang, K.,Wang, C.,Fan, Q.,Tang, X.,Zhang, X.,Wang, K.,Fu, Y.,Liang, H.
A c-di-GMP signaling module controls responses to iron in Pseudomonas aeruginosa.
Nat Commun, 15:1860-1860, 2024

PubMed Abstract: Cyclic dimeric guanosine monophosphate (c-di-GMP) serves as a bacterial second messenger that modulates various processes including biofilm formation, motility, and host-microbe symbiosis. Numerous studies have conducted comprehensive analysis of c-di-GMP. However, the mechanisms by which certain environmental signals such as iron control intracellular c-di-GMP levels are unclear. Here, we show that iron regulates c-di-GMP levels in Pseudomonas aeruginosa by modulating the interaction between an iron-sensing protein, IsmP, and a diguanylate cyclase, ImcA. Binding of iron to the CHASE4 domain of IsmP inhibits the IsmP-ImcA interaction, which leads to increased c-di-GMP synthesis by ImcA, thus promoting biofilm formation and reducing bacterial motility. Structural characterization of the apo-CHASE4 domain and its binding to iron allows us to pinpoint residues defining its specificity. In addition, the cryo-electron microscopy structure of ImcA in complex with a c-di-GMP analog (GMPCPP) suggests a unique conformation in which the compound binds to the catalytic pockets and to the membrane-proximal side located at the cytoplasm. Thus, our results indicate that a CHASE4 domain directly senses iron and modulates the crosstalk between c-di-GMP metabolic enzymes.

PubMed: 38424057
DOI: 10.1038/s41467-024-46149-3

Experimental method

ELECTRON MICROSCOPY (3.2 Å)