c-di-AMP hydrolysis by the phosphodiesterase AtaC promotes differentiation of multicellular bacteria
Open Access
- 31 March 2020
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 117 (13), 7392-7400
- https://doi.org/10.1073/pnas.1917080117
Abstract
Antibiotic-producing Streptomyces use the diadenylate cyclase DisA to synthesize the nucleotide second messenger c-di-AMP, but the mechanism for terminating c-di-AMP signaling and the proteins that bind the molecule to effect signal transduction are unknown. Here, we identify the AtaC protein as a c-di-AMP-specific phosphodiesterase that is also conserved in pathogens such as Streptococcus pneumoniae and Mycobacterium tuberculosis. AtaC is monomeric in solution and binds Mn2+ to specifically hydrolyze c-di-AMP to AMP via the intermediate 5'-pApA. As an effector of c-di-AMP signaling, we characterize the RCK_C domain protein CpeA. c-diAMP promotes interaction between CpeA and the predicted cation/ proton antiporter, CpeB, linking c-di-AMP signaling to ion homeostasis in Actinobacteria. Hydrolysis of c-di-AMP is critical for normal growth and differentiation in Streptomyces, connecting ionic stress to development. Thus, we present the discovery of two components of c-di-AMP signaling in bacteria and show that precise control of this second messenger is essential for ion balance and coordinated development in Streptomyces.Funding Information
- Deutsche Forschungsgemeinschaft (KA 730/9-1)
- Deutsche Forschungsgemeinschaft (WI 3717/3-1)
- Deutsche Forschungsgemeinschaft (TS 325/1-1, TS 325/2-1, TS 325/2-2)
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