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Updated: Aug 14, 2025

Identifying the Binding Proteins of Small Ligands with the Differential Radial Capillary Action of Ligand Assay DRaCALA
Published on: March 19, 2021
The c-di-AMP-binding protein CbpB modulates the level of ppGpp alarmone in Streptococcus agalactiae
Giovanni Covaleda-Cortés1, Ariel Mechaly2, Terry Brissac1
1Unité Biologie des Bactéries Pathogènes à Gram-positif, CNRS UMR 6047, Institut Pasteur, Université Paris Cité, France.
Abstract:
Cyclic di-AMP is an essential signalling molecule in Gram-positive bacteria. This second messenger regulates the osmotic pressure of the cell by interacting directly with the regulatory domains, either RCK_C or CBS domains, of several potassium and osmolyte uptake membrane protein systems. Cyclic di-AMP also targets stand-alone CBS domain proteins such as DarB in Bacillus subtilis and CbpB in Listeria monocytogenes. We show here that the CbpB protein of Group B Streptococcus binds c-di-AMP with a very high affinity. Crystal structures of CbpB reveal the determinants of binding specificity and significant conformational changes occurring upon c-di-AMP binding. Deletion of the cbpB gene alters bacterial growth in low potassium conditions most likely due to a decrease in the amount of ppGpp caused by a loss of interaction between CbpB and Rel, the GTP/GDP pyrophosphokinase.
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