P-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 CO concentrations, they evolved a CO-concentrating mechanism (CCM) to augment intracellular inorganic carbon (C) levels for efficient CO fixation. However, how cyanobacteria sense the fluctuation in C is poorly understood. Here we present biochemical, structural, and physiological insights into SbtB, a unique P-like signaling protein, which provides new insights into C sensing. SbtB is highly conserved in cyanobacteria and is coexpressed with CCM genes. The SbtB protein from the cyanobacterium 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 proteins. This clearly indicates that proteins of the P 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 acclimation. Collectively, our results suggest that SbtB acts as a C sensor protein via cAMP binding, highlighting an evolutionarily conserved role for cAMP in signaling the cellular carbon status.