PROSITE documentation PDOC50110

Response regulatory domain profile

Most prokaryotic signal-transduction systems and a few eukaryotic pathways use phosphotransfer schemes involving two conserved components, a histidine protein kinase (HK) (see <PDOC50109>) and a response regulator protein (RR). The HK, which is regulated by environmental stimuli, autophosphorylates at a histidine residue, creating a high-energy phosphoryl group that is subsequently transferred to an aspartate residue in the RR. Most RRs consist of two domains: a conserved N-terminal regulatory domain and a variable C-terminal effector domain. Phosphorylation of the regulatory domain induces a conformational change that results in activation of an associated domain that effects the response. The regulatory domains of RRs have three activities. First they interact with phosphorylated HKs and catalyze transfer of a phosphoryl group to one of their own Asp residues. Second, they catalyze autodephosphorylation. And finally they regulate the activities of their associated effector domains in a phosphorylation-dependent manner. The regulatory domains, often called receiver domains, can also be found within hybrid histidine kinases or as isolated proteins within phosphorelay pathways. In these contexts, the receiver domains are not physically connected to effector domains and play no direct role in regulating effector domain function.

The RR domain has a doubly wound five-stranded α/β fold consisting of about 125 residues (see <PDB:2CHY>). This fold consists a central five-stranded parallel β sheet flanked on both faces by five amphipathic α helices. Residues that are highly conserved in all RR domains are clustered in two regions: an active-site cleft formed by loops that extend from the C-terminal ends of β strands 1, 3 and 5, and a pair of residues that form a diagonal path extending across the molecule from the active site. The active site is a conserved acidic pocket and contains the phosphorylatable aspartate residue [1,2,3].

The profile we developed covers the entire RR domain.