c-di-AMP hydrolysis by the phosphodiesterase AtaC promotes differentiation of multicellular bacteria

Latoscha, Andreas; Drexler, David Jan; Al-Bassam, Mahmoud M.; Bandera, Adrian M.; Kaever, Volkhard; Findlay, Kim C.; Witte, Gregor und Tschowri, Natalia (2020): c-di-AMP hydrolysis by the phosphodiesterase AtaC promotes differentiation of multicellular bacteria. In: Proceedings of the National Academy of Sciences of the United States of America, Bd. 117, Nr. 13: S. 7392-7400

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department Biochemie
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• ISSN: 0027-8424
• Sprache: Englisch