Evolution of PII signaling superfamily

Lately, new classes of PII signaling proteins have been identified and renamed as PII-like proteins. The PII-like proteins are structurally similar and clearly related to canonical PII proteins, but lacking canonical PII PROSITE signature sequences and their functions are completely unknown. Bioinformatics and structural genomics approaches expanded the members of the PII superfamily and proposed that the PII-like proteins represent an even more widespread family of regulators than classical PII proteins. PII-like proteins are universally distributed across all domains of life, including bacteria, archaea, plants, protozoa, and animals, proposing a fundamental role in cell physiology.

Structural similarity of different classes (sequence-unrelated) of PII and PII-like signaling proteins

In our laboratory, we are exploring the molecular, structural and cellular functions of several PII-like proteins; For example:

a. PII-like protein SbtB is linking the second messenger cAMP to carbon sensation

To cope with low atmospheric CO₂ concentrations that developed over the course of evolution, cyanobacteria evolved a CO₂-concentrating mechanism (CCM), which elevates CO₂ levels in the vicinity of RubisCO, the key enzyme of CO₂ fixation. Recently, we characterized a unique component of cyanobacterial CCM, the PII-like signaling protein SbtB, which provided new insights into carbon sensing in cyanobacteria. We found that SbtB senses a variety of adenosine nucleotides, including the second messenger cAMP. Moreover, physiological and biochemical studies indicated importance of SbtB for acclimation to varying carbon regimes in the ecological niches of cyanobacteria. Therefore, PII-like protein SbtB represents a new principle of carbon sensing via second messenger cAMP binding, to regulate the cyanobacterial carbon concentrating mechanisms. However, the whole regulatory network of SbtB remains undiscovered.

Proposed model for regulatory mechanism of SbtB on HCO3- transporter SbtA

b. PII-like protein CutA is an enigmatic protein uninvolved in heavy metal sensation

The PII-like protein CutA is annotated as being involved in heavy metal tolerance. However, the precise cellular function of CutA remains unclear. Our bioinformatic analysis reveals that CutA proteins are universally distributed across all domains of life. However, we were unable to find any involvement of cyanobacterial and E. coli CutA in metal tolerance. Therefore, we concluded that CutA is involved in yet to be identified sensory function other than metal sensing. Furthermore, we resolved high-resolution CutA structures from cyanobacterial Nostoc sp. and Synechococcus elongatus. Intriguingly, the clefts between the CutA subunits, corresponding to the binding pockets of canonical PII proteins, are formed by conserved aromatic and charged residues, suggesting a conserved binding/signaling function for CutA proteins. However, the natural CutA ligands remain to be identified.

For recent publications see list of publications (https://pubmed.ncbi.nlm.nih.gov/?term=Selim+KA&cauthor_id=32077495)