A catalogue of signal molecules that interact with sensor kinases, chemoreceptors and transcriptional regulators

Bacteria have evolved many different signal transduction systems that sense signals and generate a variety of responses. Generally, most abundant are transcriptional regulators, sensor histidine kinases and chemoreceptors. Typically, these systems recognize their signal molecules with dedicated ligand-binding domains (LBDs), which, in turn, generate a molecular stimulus that modulates the activity of the output module. There are an enormous number of different LBDs that recognize a similarly diverse set of signals. To give a global perspective of the signals that interact with transcriptional regulators, sensor kinases and chemoreceptors, we manually retrieved information on the protein-ligand interaction from about 1,200 publications and 3D structures. The resulting 811 proteins were classified according to the Pfam family into 127 groups. These data permit a delineation of the signal profiles of individual LBD families as well as distinguishing between families that recognize signals in a promiscuous manner and those that possess a well-defined ligand range. A major bottleneck in the field is the fact that the signal input of many signaling systems is unknown. The signal repertoire reported here will help the scientific community design experimental strategies to identify the signaling molecules for uncharacterised sensor proteins. The authors have compiled the information on the interaction of signal molecules with sensor kinases, chemoreceptors and transcriptional regulators.

Automated summary

Bacteria have developed various signal transduction systems to sense and respond to signals, with transcriptional regulators, sensor histidine kinases, and chemoreceptors being the most prevalent. These systems use ligand-binding domains (LBDs) to recognize signal molecules and modulate the activity of the output module. By manually retrieving information from publications and 3D structures, the authors classified 811 proteins, revealing the signal profiles and distinguishing between families with promiscuous signal recognition and those with well-defined ligand ranges. This signal repertoire will aid in identifying signaling molecules for uncharacterised sensor proteins.