The HAMP domain (present in Histidine kinases, Adenyl cyclases, Methyl-accepting proteins and Phosphatases) is an approximately 50-amino acid α-helical region common to chemoreceptors and histidine kinases that is present in several multidomain sensor proteins that participate in a variety of signal transduction processes. It is found in bacterial sensor and chemotaxis proteins and in eukaryotic histidine kinases. The bacterial proteins are usually integral membrane proteins and part of a two-component signal transduction pathway. One or several copies of the HAMP domain can be found in association with other domains, such as the histidine kinase domain, the bacterial chemotaxis sensory transducer domain, the PAS repeat, the EAL domain, the GGDEF domain, the protein phosphatase 2C-like domain, the guanylate cyclase domain, or the response regulatory domain. It has been suggested that the HAMP domain possesses a role of regulating the phosphorylation or methylation of homodimeric receptors by transmitting the conformational changes in periplasmic ligand-binding domains to cytoplasmic signalling kinase and methyl-acceptor domains [, , ].
Aer2 soluble receptor from Pseudomonas aeruginosa contains three successive HAMP domains in the N-terminal region. HAMP domains are widespread prokaryotic signaling modules. This entry is the third N-terminal HAMP domain (HAMP3). HAMP3 adopts a conformation resembling Af1503, with only minor differences in helical tilt and orientation []. The basic construction of each HAMP domain consists of a monomeric unit of two parallel α-helices (AS1 and AS2) joined by an elongated connector of 12-14 residues form a parallel four-helix bundle [].
TorS is part of the trimethylamine-N-oxide (TMAO) reductase (Tor) pathway, which consists TorT, a periplasmic binding protein that binds TMAO; TorS, a sensor histidine kinase that forms a complex with TorT, and TorR, the response regulator. The Tor pathway is involved in regulating a cellular response to trimethylamine-N-oxide (TMAO), a terminal electron receptor in anaerobic respiration [, , , ]. TorS consists of a periplasmic sensor domain, as well as a HAMP domain, a histidine kinase domain, and a receiver domain [, ].
TorS is part of the trimethylamine-N-oxide (TMAO) reductase (Tor) pathway, which consists TorT, a periplasmic binding protein that binds TMAO; TorS, a sensor histidine kinase that forms a complex with TorT, and TorR, the response regulator. The Tor pathway is involved in regulating a cellular response to trimethylamine-N-oxide (TMAO), a terminal electron receptor in anaerobic respiration [, , , ]. TorS consists of a periplasmic sensor domain, as well as a HAMP domain, a histidine kinase domain, and a receiver domain [, ].
This entry represents a four-helix bundle that operates as a ubiquitous sensory module in prokaryotic signal-transduction, which is known as four-helix bundles methyl-accepting chemotaxis protein (4HB_MCP) domain. The 4HB_MCP is always found between two predicted transmembrane helices indicating that it detects only extracellular signals. In many cases the domain is associated with a cytoplasmic HAMP domain suggesting that most proteins carrying the bundle might share the mechanism of transmembrane signalling which is well-characterised in E coli chemoreceptors [].This domain is found in a group of methyl-accepting chemotaxis receptors that includes Vibrio cholerae HlyB [].
Archaebacterial photoreceptors mediate phototaxis by regulating cell motility through two-component signaling cascades like those found in chemotaxis signaling chains of enteric bacteria. The photoreceptor sensory rhodopsin II from N. pharaonis (NpSRII) in complex with its cognate transducer NpHtrII serves as a system for transmembrane signal transfer. This entry is for the transmembrane domain of the transducer HtrII. Studies suggest that conformation changes of the NpSRII/NpHtrII complex may be crucial for the mechanism of signal propagation spanning the membrane domain and feeding into the HAMP domain []. Furthermore, HtrII in H. salinarum not only transmits the signal from the photoreceptor SRII but also operates as a chemoreceptor.
The GGDEF domain, which has been named after the conserved central sequence pattern GG[DE][DE]F is widespread in prokaryotes. It is typically present in multidomain proteins containing regulatory domains of signaling pathways or protein-protein or protein-ligand interaction modules, such as the response regulatory domain, the PAS/PAC domain, the HAMP domain, the GAF domain, the FHA domain or the TPR repeat. However a few single-domain proteins are also known. The GGDEF domain is involved in signal transduction and is likely to catalyze synthesis or hydrolysis of cyclic diguanylate (c-diGMP, bis(3',5')-cyclic diguanylic acid), an effector molecule that consists of two cGMP moieties bound head-to-tail [, , ].Structural studies of PleD from Caulobacter crescentus show that this domain forms a five-stranded beta sheet surrounded by helices, similar to the catalytic core of adenylate cyclase [].
The nitrate and nitrite-sensing (NIT) domain is a (~250 aa) sensor domain found in various receptor components of signal transduction pathways from different bacterial lineages []. Proteins containing a NIT domain belong to one of four known classes of prokaryotic signal transduction proteins: intracellular transcription anti-termination regulators, sensor histidine kinases, methyl-accepting chemotaxis proteins, diguanylate cyclases/phosphodiesterases. NIT-containing receptors regulate cellular functions such as gene expression (transcription anti-terminators and histidine kinases), cell motility (chemotaxis receptors), and enzyme activity (diguanylate cyclases/phosphodiesterases), in response to changes in nitrate and/or nitrite concentrations. The NIT domain is found as both an extracellular and an intracellular sensor. The NIT domain can be found in combination with other signalling domains, such as ANTAR, HAMP (), MCP, Hemerythrins (), CHASE (), GGDEF (), PAS (), EAL (), HK (), GAF, REC and Hpt ().This entry represents a subgroup found exclusively in bacteria.
The nitrate and nitrite-sensing (NIT) domain is a (~250 aa) sensor domain found in various receptor components of signal transduction pathways from different bacterial lineages []. The NIT domain is predicted to be all α-helical in structure []. Proteins containing a NIT domain belong to one of four known classes of prokaryotic signal transduction proteins: intracellular transcription anti-termination regulators, sensor histidine kinases, methyl-accepting chemotaxis proteins, diguanylate cyclases/phosphodiesterases. NIT-containing receptors regulate cellular functions such as gene expression (transcription anti-terminators and histidine kinases), cell motility (chemotaxis receptors), and enzyme activity (diguanylate cyclases/phosphodiesterases), in response to changes in nitrate and/or nitrite concentrations. The NIT domain is found as both an extracellular and an intracellular sensor. The NIT domain can be found in combination with other signalling domains, such as ANTAR, HAMP (), MCP, Hemerythrins (), CHASE (), GGDEF (), PAS (), EAL (), HK (), GAF, REC and Hpt ().
Methyl-accepting chemotaxis proteins (MCPs) are a family of bacterial receptors that mediate chemotaxis to diverse signals, responding to changes in the concentration of attractants and repellents in the environment by altering swimming behaviour []. Environmental diversity gives rise to diversity in bacterial signalling receptors, and consequently there are many genes encoding MCPs []. For example, there are four well-characterised MCPs found in Escherichia coli: Tar (taxis towards aspartate and maltose, away from nickel and cobalt), Tsr (taxis towards serine, away from leucine, indole and weak acids), Trg (taxis towards galactose and ribose) and Tap (taxis towards dipeptides). MCPs share similar topology and signalling mechanisms. MCPs either bind ligands directly or interact with ligand-binding proteins, transducing the signal to downstream signalling proteins in the cytoplasm. MCPs undergo two covalent modifications: deamidation and reversible methylation at a number of glutamate residues. Attractants increase the level of methylation, while repellents decrease it. The methyl groups are added by the methyl-transferase cheR and are removed by the methylesterase cheB. Most MCPs are homodimers that contain the following organisation: an N-terminal signal sequence that acts as a transmembrane domain in the mature protein; a poorly-conserved periplasmic receptor (ligand-binding) domain; a second transmembrane domain; and a highly-conserved C-terminal cytoplasmic domain that interacts with downstream signalling components. The C-terminal domain contains the glycosylated glutamate residues. This entry represents the ligand-binding domain found in a number of methyl-accepting chemotaxis receptors, such as E.coli Tar (taxis to aspartate and repellents), which is a receptor for the attractant L-aspartate [, ]. It is a homodimeric receptor that contains an N-terminal periplasmic ligand binding domain, a transmembrane region, a HAMP domain and a C-terminal cytosolic signaling domain [].
This entry represents a four-helix bundle that operates as a ubiquitous sensory module in prokaryotic signal-transduction, which is known as four-helix bundles methyl-accepting chemotaxis protein (4HB_MCP) domain. The 4HB_MCP is always found between two predicted transmembrane helices indicating that it detects only extracellular signals. In many cases the domain is associated with a cytoplasmic HAMP domain suggesting that most proteins carrying the bundle might share the mechanism of transmembrane signalling which is well-characterised in E coli chemoreceptors [].Methyl-accepting chemotaxis proteins (MCPs) are a family of bacterial receptors that mediate chemotaxis to diverse signals, responding to changes in the concentration of attractants and repellents in the environment by altering swimming behaviour []. Environmental diversity gives rise to diversity in bacterial signalling receptors, and consequently there are many genes encoding MCPs []. For example, there are four well-characterised MCPs found in Escherichia coli: Tar (taxis towards aspartate and maltose, away from nickel and cobalt), Tsr (taxis towards serine, away from leucine, indole and weak acids), Trg (taxis towards galactose and ribose) and Tap (taxis towards dipeptides). MCPs share similar topology and signalling mechanisms. MCPs either bind ligands directly or interact with ligand-binding proteins, transducing the signal to downstream signalling proteins in the cytoplasm. MCPs undergo two covalent modifications: deamidation and reversible methylation at a number of glutamate residues. Attractants increase the level of methylation, while repellents decrease it. The methyl groups are added by the methyl-transferase cheR and are removed by the methylesterase cheB. Most MCPs are homodimers that contain the following organisation: an N-terminal signal sequence that acts as a transmembrane domain in the mature protein; a poorly-conserved periplasmic receptor (ligand-binding) domain; a second transmembrane domain; and a highly-conserved C-terminal cytoplasmic domain that interacts with downstream signalling components. The C-terminal domain contains the glycosylated glutamate residues.
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 [, ].Signal transducing histidine kinases are the key elements in two-component signal transduction systems, which control complex processes such as the initiation of development in microorganisms [, ]. Examples of histidine kinases are EnvZ, which plays a central role in osmoregulation [], and CheA, which plays a central role in the chemotaxis system []. Histidine kinases usually have an N-terminal ligand-binding domain and a C-terminal kinase domain, but other domains may also be present. The kinase domain is responsible for the autophosphorylation of the histidine with ATP, the phosphotransfer from the kinase to an aspartate of the response regulator, and (with bifunctional enzymes) the phosphotransfer from aspartyl phosphate back to ADP or to water []. The kinase core has a unique fold, distinct from that of the Ser/Thr/Tyr kinase superfamily. HKs can be roughly divided into two classes: orthodox and hybrid kinases [, ]. Most orthodox HKs, typified by the Escherichia coli EnvZ protein, function as periplasmic membrane receptors and have a signal peptide and transmembrane segment(s) that separate the protein into a periplasmic N-terminal sensing domain and a highly conserved cytoplasmic C-terminal kinase core. Members of this family, however, have an integral membrane sensor domain. Not all orthodox kinases are membrane bound, e.g., the nitrogen regulatory kinase NtrB (GlnL) is a soluble cytoplasmic HK []. Hybrid kinases contain multiple phosphodonor and phosphoacceptor sites and use multi-step phospho-relay schemes instead of promoting a single phosphoryl transfer. In addition to the sensor domain and kinase core, they contain a CheY-like receiver domain and a His-containing phosphotransfer (HPt) domain.This entry represents TorS proteins, which are part of a regulatory system for the torCAD operon that encodes the pterin molybdenum cofactor-containing enzyme trimethylamine-N-oxide (TMAO) reductase (TorA), a cognate chaperone (TorD), and a penta-haem cytochrome (TorC). TorS works together with the inducer-binding protein TorT and the response regulator TorR. TorS contains histidine kinase ATPase (), HAMP (), phosphoacceptor (), and phosphotransfer () domains and a response regulator receiver domain ().
