| Primary Identifier | IPR008327 | Type | Family |
| Short Name | Sig_transdc_resp-reg_antiterm |
| description | Two-component signal transduction systems enable bacteria to sense, respond, and adapt to a wide range of environments, stressors, and growth conditions []. Some bacteria can contain up to as many as 200 two-component systems that need tight regulation to prevent unwanted cross-talk []. These pathways have been adapted to response to a wide variety of stimuli, including nutrients, cellular redox state, changes in osmolarity, quorum signals, antibiotics, and more []. Two-component systems are comprised of a sensor histidine kinase (HK) and its cognate response regulator (RR) []. The HK catalyses its own auto-phosphorylation followed by the transfer of the phosphoryl group to the receiver domain on RR; phosphorylation of the RR usually activates an attached output domain, which can then effect changes in cellular physiology, often by regulating gene expression. Some HK are bifunctional, catalysing both the phosphorylation and dephosphorylation of their cognate RR. The input stimuli can regulate either the kinase or phosphatase activity of the bifunctional HK.A variant of the two-component system is the phospho-relay system. Here a hybrid HK auto-phosphorylates and then transfers the phosphoryl group to an internal receiver domain, rather than to a separate RR protein. The phosphoryl group is then shuttled to histidine phosphotransferase (HPT) and subsequently to a terminal RR, which can evoke the desired response [, ].This entry represents response regulators (RRs) with a CheY-like receiver domain fused to an RNA-binding C-terminal ANTAR domain (AmiR-like) that affects antitermination.Expression of the aliphatic amidase operon in Pseudomonas aeruginosa is controlled by an antitermination mechanism involving the AmiR/AmiC system. In the presence of small-molecule inducers, such as acetamide, premature termination is prevented by AmiR, which interacts with the nascent mRNA upstream of the terminator and probably prevents formation of the stem-loop. In the absence of inducers, the antitermination activity of AmiR is inhibited by interaction with AmiC [].Response regulators of the microbial two-component signal transduction systems typically consist of an N-terminal CheY-like receiver (phosphoacceptor) domain and a C-terminal output (usually DNA-binding) domain. In response to an environmental stimulus, a phosphoryl group is transferred from the His residue of sensor histidine kinase to an Asp residue in the CheY-like receiver domain of the cognate response regulator [, , ]. Phosphorylation of the receiver domain induces conformational changes that activate an associated output domain, which in turn triggers the response. Phosphorylation-induced conformational changes in response regulator molecule have been demonstrated in direct structural studies [].AmiR differs from the rest of the members of this group in that none of the residues involved in regulation by phosphorylation are conserved, despite the high structural homology of its N terminus to the CheY-like receiver domains. This suggests that phosphorylation plays no role in its regulation. Indeed, it has been shown that, unlike classical RRs, it is instead controlled via ligand-regulated sequestration by AmiC [, ].The C-terminal output domain of the members of this group is the RNA-binding antiterminator domain ANTAR () [, , ]. Superficially, the coiled-coil and three-helix bundle that form this domain in AmiR []appear radically different from the compact HTH DNA-binding domain of the NarL protein. However, the last three helices in AmiR are very similar in length and hydropathy profiles to those of NarL and its homologues, and are arranged in a very similar topology, suggesting an evolutionary relationship []. These C-terminal helices of AmiR appear to be essential for its transcription antitermination activity []. However, helix-turn-helix domains like those in NarL or OmpR []are adapted to sequence-specific binding in the major groove of double-stranded B-form DNA. It is not clear how such a structure might function in a protein whose role is to prevent the formation of a termination stem-loop structure, by binding single-stranded RNA []. |
