Nikon PostDoc Award:
Cross-talk between cAMP and c-di-AMP signaling via carbon sensor protein SbtB: Linking CO2 homeostasis with diurnal metabolic switch

Khaled Selim

Khaled Selim1, Michael Haffner1, Martin Hagemann2, Karl Forchhammer1

1Tübingen Uni, Tübingen, Germany,
2Rostock Uni, Rostock, Germany

PII superfamily consists of widespread signal transduction proteins found in all domains of life. In addition to canonical PII proteins involved in C/N sensing, structurally similar PII-like proteins evolved to fulfill diverse, yet poorly understood cellular functions. For efficient CO2 fixation at low ambient concentrations, cyanobacteria evolved highly specialized carbon concentrating mechanism, to augment intracellular inorganic carbon (Ci) levels. Recently, we identified the PII- like protein SbtB as Ci sensing module via sensing various adenine nucleotides including the second messenger nucleotides cAMP, and c-di-AMP, involved in global cellular homeostasis. We showed that cAMP acts as carbon signal, whereas adenyl-nucleotide binding links SbtB signalling to the energy state of the cells. The c-di-AMP signaling through SbtB turned out pivotal for day-night acclimation of cyanobacteria via regulation of glycogen metabolism. To our knowledge, this is the first signaling protein known integrating both cAMP and c-di-AMP signaling. Moreover, SbtB possess a C-terminal extension with a disulfide bridge, which we call R-loop. We revealed an unusual ATP/ADP apyrase activity of SbtB that is controlled by the R- loop. We followed the sequence of the hydrolysis reactions from ATP to AMP in crystallographic snapshots and revealed the structural mechanism by which changes of the R-loop redox state modulate apyrase activity. This highlights SbtB as a central switch-point in cyanobacterial cell physiology, integrating not only signals from the energy state (adenyl-nucleotide binding) and the carbon supply via cAMP binding, but also from the diurnal status reported by the R-loop redox-switch and c-di-AMP binding.

 

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