P_II-like signaling protein SbtB links cAMP sensing with cyanobacterial inorganic carbon response

Cyanobacteria are phototrophic prokaryotes that evolved oxygenic photosynthesis ∼2.7 billion y ago and are presently responsible for ∼10% of total global photosynthetic production. To cope with the evolutionary pressure of dropping ambient CO₂ concentrations, they evolved a CO₂-concentrating mechanism (CCM) to augment intracellular inorganic carbon (C_i) levels for efficient CO₂ fixation. However, how cyanobacteria sense the fluctuation in C_i is poorly understood. Here we present biochemical, structural, and physiological insights into SbtB, a unique P_II-like signaling protein, which provides new insights into C_i sensing. SbtB is highly conserved in cyanobacteria and is coexpressed with CCM genes. The SbtB protein from the cyanobacterium Synechocystis sp. PCC 6803 bound a variety of adenosine nucleotides, including the second messenger cAMP. Cocrystal structures unraveled the individual binding modes of trimeric SbtB with AMP and cAMP. The nucleotide-binding pocket is located between the subunit clefts of SbtB, perfectly matching the structure of canonical P_II proteins. This clearly indicates that proteins of the P_II superfamily arose from a common ancestor, whose structurally conserved nucleotide-binding pocket has evolved to sense different adenyl nucleotides for various signaling functions. Moreover, we provide physiological and biochemical evidence for the involvement of SbtB in C_i acclimation. Collectively, our results suggest that SbtB acts as a C_i sensor protein via cAMP binding, highlighting an evolutionarily conserved role for cAMP in signaling the cellular carbon status.