Two-component signal transduction

Most prokaryotic signal-transduction systems and a few eukaryotic pathways use phosphotransfer schemes involving two conserved components, a histidine protein kinase and a response regulator protein. The histidine protein kin ase, which is regulated by environmental stimuli, autophosphorylates at a h istidine residue, creating a high-energy phosphoryl group that is subsequen tly transferred to an aspartate residue in the response regulator protein. Phosphorylation induces a conformational change in the regulatory domain th at results in activation of an associated domain that effects the response. The basic scheme is highly adaptable, and numerous variations have provide d optimization within specific signaling systems. The domains of two-compon ent proteins are modular and can be integrated into proteins and pathways i n a variety of ways, but the core structures and activities are maintained. Thus detailed analyses of a relatively small number of representative prot eins provide a foundation for understanding this large family of signaling proteins.