Functional diversity of c-di-GMP receptors in prokaryotic and eukaryotic systems

Cyclic bis-(3', 5')-dimeric guanosine monophosphate (c-di-GMP) is ubiquitous in many bacterial species, where it functions as a nucleotide-based secondary messenger and is a vital regulator of numerous biological processes. Due to its ubiquity, most bacterial species possess a wide range of downstream receptors that has a binding affinity to c-di-GMP and elicit output responses. In eukaryotes, several enzymes and riboswitches operate as receptors that interact with c-di-GMP and transduce cellular or environmental signals. This review examines the functional variety of receptors in prokaryotic and eukaryotic systems that exhibit distinct biological responses after interacting with c-di-GMP. Evolutionary relationships and similarities in distance among the c-di-GMP receptors in various bacterial species were evaluated to understand their specificities. Furthermore, residues of receptors involved in c-di-GMP binding are summarized. This review facilitates the understanding of how distinct receptors from different origins bind c-di-GMP equally well, yet fulfill diverse biological roles at the interspecies, intraspecies, and interkingdom levels. Furthermore, it also highlights c-di-GMP receptors as potential therapeutic targets, particularly those found in pathogenic microorganisms.C5iF5BkbNAVqYPEX5S1oMBVideo Abstract

Automated summary

This review examines the functional diversity of receptors in prokaryotic and eukaryotic systems that exhibit distinct biological responses after interacting with c-di-GMP. Evolutionary relationships and similarities in distance among the c-di-GMP receptors in various bacterial species were evaluated to understand their specificities. Furthermore, residues of receptors involved in c-di-GMP binding are summarized. The research facilitates the understanding of how distinct receptors from different origins bind c-di-GMP equally well, yet fulfill diverse biological roles at different levels, and highlights the importance of c-di-GMP receptors as potential therapeutic targets.