Abstract
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(2) concentrations, they evolved a CO(2)-concentrating mechanism (CCM) to augment intracellular inorganic carbon (C(i)) levels for efficient CO(2) 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.