Response regulator receiver domain (REC domain)

The response regulator receiver (REC) domain is a conserved protein module found primarily in bacteria, serving as the phosphoacceptor in two-component signaling systems (TCS) (UniProt: IPR001789). These domains function by receiving a phosphate group from a cognate histidine kinase onto a conserved aspartate residue, which triggers a conformational change that activates an associated output domain, often a DNA-binding transcription factor (PubMed: 24103353). Because TCS are essential for bacterial survival, virulence, and antibiotic resistance, and are notably absent in mammalian cells, the REC domain is a high-priority target for the development of novel antibacterial agents (PubMed: 28943388). Therapeutic strategies focus on small molecules that inhibit the phosphorylation cycle or prevent the dimerization required for downstream signaling (PubMed: 30254014). While no REC-specific inhibitors are currently in widespread clinical use as primary antibacterials, compounds like the anthelmintic closantel and experimental inhibitors like Savirin have demonstrated the potential of targeting these domains to treat multi-drug resistant infections (PubMed: 10490504, PubMed: 24532631).

Other names

REC domainCheY-homologous domainReceiver domainPhosphoacceptor domainTwo-component system response regulator receiver domain

Inhibition of phosphorylation at the conserved aspartate residue, disruption of dimerization, or competitive binding to the active site to prevent signal transduction.