8Z6N

The dimerization structure of CHASE4 domain of PA2072 (alpha form)

Summary for 8Z6N

• Entry DOI: 10.2210/pdb8z6n/pdb
• Descriptor: Bifunctional diguanylate cyclase/phosphodiesterase (2 entities in total)
• Functional Keywords: signaling protein
• Biological source: Pseudomonas aeruginosa PAO1
• Total number of polymer chains: 1
• Total formula weight: 23716.35

Authors

Zhang, Y.,Lin, Z.,Xiao, Y.J. (deposition date: 2024-04-19, release date: 2025-04-23, Last modification date: 2025-11-12)

Primary citation

Zhang, Y.,Gao, X.,Xiao, Y.,Duan, Y.,Xiao, W.,Xu, Y.,Yang, T.,Zhang, H.,Chen, C.,Shi, S.,Su, X.C.,Jin, X.,Zhao, J.,Yang, H.,Yin, G.,Yuan, W.,Wang, Z.,Huang, W.,Lin, Z.
eATP sensing by the purinergic receptor PA2072 for allosteric modulation in intracellular c-di-GMP signaling.
Proc.Natl.Acad.Sci.USA, 122:e2423664122-e2423664122, 2025

PubMed Abstract: Extracellular ATP (eATP) has emerged as a crucial signaling molecule across eukaryotic and prokaryotic domains, modulating diverse cellular functions by activating purinergic receptors to initiate intracellular signaling cascades. However, the structural and molecular mechanisms underlying eATP sensing and signaling by prokaryotic receptors remain largely unknown. Here, we demonstrate that the receptor PA2072 in is responsible for recognizing eATP to down-regulate intracellular cyclic di-GMP levels. The periplasmic CHASE4 domain of PA2072 specifically binds and hydrolyzes eATP, exhibiting ATPase activity both in the presence and absence of a divalent cation cofactor. Structural elucidation of the PA2072 CHASE4 domain in its monomeric and complex states unveils an exquisite molecular switch governed by the oligomeric state. ATP hydrolysis by the catalytically active monomeric form is coupled to homodimerization, concomitantly deactivating its ATPase activity and initiating intracellular phosphodiesterase activity. These findings open avenues for understanding interkingdom eATP signaling and developing targeted therapeutic interventions.

PubMed: 41187079
DOI: 10.1073/pnas.2423664122

Experimental method

X-RAY DIFFRACTION (2.39 Å)