LAUSR

Significance The dCache shows a ubiquitous phylogenetic distribution and is abundantly present in archaea, bacteria, and eukaryota. It’s the predominant bacterial extracytosolic sensor domain and present in all major families of transmembrane receptors. Most characterized dCache mediate responses to diversely similar ligands, which were found to bind to the membrane-distal module. Although there’s also evidence that other dCache respond to multiple ligands, the information on the corresponding molecular mechanism is currently limited. We show here that the capacity to respond to multiple ligands is due to the utilization of both dCache modules. This work provides information on the forces that have led to the evolution of dCache domains and provides features that characterize receptors with narrow and broad ligand ranges.