Histidine kinases
| Histidine kinases | ||
|---|---|---|
| Enzyme classification | ||
| EC, category | 2.7.13.- , kinase | |
| Substrate | ATP + protein L-histidine | |
| Products | ADP + protein-N-phospho-L-histidine | |
Histidine kinases (also called protein histidine kinases ) are enzymes that phosphorylate histidine residues in proteins . They are part of signal transduction cascades , that is, they register signals and then trigger a response specific to this signal. Histidine kinases occur in prokaryotes ( i.e. archaebacteria and eubacteria ), in fungi and in the plant kingdom. Only in animals including humans - except in the mitochondria - no histidine kinases have been discovered to date. They have a lot in common with serine kinases .
The mode of action of histidine kinases is divided into two systems:
- the two-component histidine kinase system
- the phosphorelay system.
The two-component histidine kinase system
The two-component histidine kinase system is one of the simplest signal transduction pathways . It is based on two enzymes, a histidine kinase and a response regulator. The histidine kinase always consists of two identical units ( monomers ) and is therefore referred to as a homodimer . It generally has three domains :
- a sensor domain,
- a phosphotransfer domain and
- an ATP binding domain.
The response regulator is a protein that consists of two domains:
- a phosphoacceptor domain and
- a regulator domain.
In signal transduction, a signal is bound by the sensor domain. The ATP of the ATP binding domain is then hydrolyzed to adenosine diphosphate (ADP) , which can no longer be bound by the ATP binding domain. It is replaced by a fresh ATP. The phosphate released during hydrolysis is transferred to a special histidine in the phosphotransfer domain. The phosphate comes from the ATP bound to the other monomer. Strictly speaking, it is therefore not a pure autophosphorylation because the other monomer is phosphorylated. The resulting phosphorylated histidine has a high phosphoryl group transfer potential ; H. it can transfer the phosphate to other amino acids very easily and without further ATP hydrolysis. This phosphate is transferred to a specific aspartate in the phosphoacceptor domain of the response regulator. The histidine kinase and the response regulator must be in close proximity for this reaction. By phosphorylating the response regulator, it changes the spatial arrangement of its amino acids. So there is a so-called conformational change . This exposes the active center of the response regulator, which can now perform its function.
The two-component histidine kinase system is found almost exclusively in the prokaryotic kingdom, less often in eukaryotes . It is incorporated into many important metabolic processes , such as the detection of certain chemical substances in Escherichia coli , which u. a. is of importance for chemotaxis .
The phosphorelay system
The Phosphorelay system is a more complex variant of the two-component histidine kinase system. It consists not only of a histidine kinase and a response regulator, but also of a regulator and a phosphotransfer protein. The phosphorylation stages are run through twice. This involves phosphorylation of one histidine in the histidine kinase, followed by transfer to the regulatory protein and subsequent phosphorylation of a second histidine, which this time is found in the phosphotransfer protein. This phosphorylation requires energy, which is provided by the hydrolysis of another ATP molecule. In the last step, the phosphate is transferred to the response regulator. Due to the necessary spatial proximity for these reactions, the histidine kinase and regulator protein , sometimes also the phosphotransfer protein, are fused with one another due to evolution ( hybrid protein ). This can be seen in Figure Part B. The phosphorelay is more common in eukaryotes than in prokaryotes . Just like the two-component histidine kinase system, the Phosphorelay is involved in important metabolic processes, such as the sporulation of Bacillus subtilis .
Diversity in function and number of histidine kinases
As already mentioned, histidine kinases are involved in many metabolic processes, such as B .:
- in the case of some fungi in the synthesis of antibiotics ,
- in bacteria in the nitrogen balance and chemotaxis ( Escherichia coli ),
- in Arabidopsis at the ethylene reception and also serves as a cytokinin receptor (hybrid kinase)
- in yeast ( Saccharomyces cerevisiae ) on the osmoregulation or
- in symbioses and nodule formation .
The number of histidine kinases in the genome of different organisms is not always the same. It varies from none ( Mycoplasma genitalium ) to over 30 (e.g. in E. coli ). There is only speculation about the correlation, i.e. the connection, the number of histidine kinases and the way of life of the organisms. For example, it is assumed that species that are constantly exposed to major changes in their environment (as is the case with E. coli : it lives or survives in the blood plasma, in the intestine, in the sewer, etc.) also have more histidine kinases than organisms, who live in constant milieus .
General structure of the histidine kinases
Proteins are always described from the N-terminus to the C-terminus , including the histidine kinases. The above-mentioned sensor domain is located at the N terminus. It can consist of various preserved motifs. Conserved motifs are understood to mean the same or mostly similar sequence of different amino acids in the sequence of several proteins. More emphasis is placed on the properties of the amino acids, such as hydrophobicity or charge . There are innumerable motives like this. The so-called GAF , PAS and HAMP motifs as well as transmembrane domains are found in the sensor domain of many histidine kinases . These domains or motifs can recognize different signals and are responsible, among other things, for the variety of histidine kinases.
The phosphotransfer and ATP binding domains are much more conserved. This means that histidine kinases from the most varied of organisms, even if they are evolutionarily very far apart, have a very great similarity, if not identical, amino acid sequence in this area. These domains were divided into different motifs based on their function. The motifs are listed in the table below. The capital letters indicate amino acids according to the one -letter code . The small h stands for any hydrophobic amino acid and the x for any x. The many non-conserved amino acids simply mean that the specific amino acids have a defined distance from one another.
| H box | Fhxxh- (S / T / A) -H- (D / E) -h- (R / K) -TPLxxh | |
| X box | many hydrophobic amino acids | |
| N-box | (D / N) -xxxhxxhhxNLhxNAhx- (F / H / Y) - (S / T) | |
| D and F box | hxhxhxDxGxGhxxxxxxxhF-xxF | |
| G-box | GGxGLGLxhhxxhhxxxxGxh-xhxxxxGxxF |
The H-box is named after the functionally important amino acid histidine, which is phosphorylated. The X-Box is responsible for the dimerization , that is, it binds the other monomer. The N-box forms a pocket through which the phosphate is conducted from the ATP to the histidine. The D-Box binds the ATP via electrostatic interactions , while the G-Box forms a kind of lid on the ATP.
literature
- Grebe, TW; Stock, JB: The Histidine Protein Kinase Superfamily. Adv. Micr. Phys. 41: 139-224 (1999)
- High, YES: Two-component and phosphorelay signal transduction. Curr. Opin. in Microbiol. 3: 165-170 (2000)
- Catlett, NL; Yoder, OC; Turgeon, BG: Whole-Genome Analysis of Two-Component Signal Transduction Genes in Fungal Pathogens. Eukar. Cell 2: 1151-1161 (2003)