The c-di-AMP-binding protein CbpB modulates the level of ppGpp alarmone in Streptococcus agalactiae.
Giovanni Covaleda-CortésAriel MechalyTerry BrissacHeike BaehreLaura DevauxPatrick EnglandBertrand RaynalSylviane HoosMyriam GominetArnaud FironPatrick Trieu-CuotPierre Alexandre KaminskiPublished in: The FEBS journal (2023)
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.
Keyphrases
- protein kinase
- biofilm formation
- binding protein
- pseudomonas aeruginosa
- candida albicans
- staphylococcus aureus
- bacillus subtilis
- listeria monocytogenes
- escherichia coli
- single cell
- genome wide
- cystic fibrosis
- molecular dynamics
- cell therapy
- gene expression
- protein protein
- molecular dynamics simulations
- bone marrow
- gram negative