Histidine phosphotransfer domain
| Histidine phosphotransfer domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 The crystal structure of the yeast histidine phosphotransferase protein Ypd1. The four helices shown in yellow comprise the conserved four-helix bundle typical of monomeric HPt domains; the helices shown in red are insertions specific to Ypd1. The histidine phosphorylation site is shown in green. From PDB: 1C02.[1] | |||||||||
| Identifiers | |||||||||
| Symbol | Hpt | ||||||||
| Pfam | PF01627 | ||||||||
| InterPro | IPR008207 | ||||||||
| SMART | HPT | ||||||||
| PROSITE | PS50894 | ||||||||
| |||||||||
| Histidine phosphotransferase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 The crystal structure of the Caulobacter crescentus histidine phosphotransferase protein ChpT in dimeric form. The four helices shown in yellow comprise the conserved four-helix bundle, with the histidine phosphorylation sites highlighted in green. The domains shown in red and tan are pseudo-CA domains that resemble the ATP-binding domains of histidine kinases, but do not bind or hydrolyze ATP. From PDB: 4FMT.[2] | |||||||||
| Identifiers | |||||||||
| Symbol | HPTransfase | ||||||||
| Pfam | PF10090 | ||||||||
| InterPro | IPR018762 | ||||||||
| |||||||||
Histidine phosphotransfer domains and histidine phosphotransferases (both often abbreviated HPt) are
aspartate residue on an intermediate "receiver" domain, typically part of a hybrid histidine kinase, to an aspartate on a final response regulator
.
Function
In orthodox two-component signaling, a
aspartate residue on the receiver domain of a response regulator. In phosphorelays, the "hybrid" histidine kinase contains an internal aspartate-containing receiver domain to which the phosphoryl group is transferred, after which an HPt protein containing a phosphorylatable histidine receives the phosphoryl group and finally transfers it to the response regulator. The relay system thus progresses in the order His-Asp-His-Asp, with the second His contributed by Hpt.[3][4][5] In some cases, a phosphorelay system is constructed from four separate proteins rather than a hybrid histidine kinase with an internal receiver domain, and in other examples both the receiver and the HPt domains are present in the histidine kinase polypeptide chain.[6]: 198 A census of two-component system domain architecture found that HPt domains in bacteria are more common as domains of larger proteins than they are as individual proteins.[4]
Regulation
The increased complexity of the phosphorelay system compared to orthodox two-component signaling provides additional opportunities for regulation and improves the specificity of the response.sporulation pathway in Bacillus subtilis, which can give rise to complex temporal variations.[8] In some known cases, there is an additional form of regulation in phosphohistidine phosphatase enzymes that act on HPt, such as the Escherichia coli protein SixA which targets ArcB.[6]: 206
Structure
The histidine phosphotransfer function can be carried out by proteins with at least two different architectures, both composed of a
sporulation factor Spo0B or the Caulobacter crescentus protein ChpT, the bundle is assembled as a protein dimer, with similarity to the structure of histidine kinases.[7][2] Monomeric HPt domains possess only one phosphorylatable histidine residue and interact with one response regulator, whereas dimers have two phosphorylation sites and can interact with two response regulators at the same time. Monomeric HPt domains have no enzymatic activity of their own and act purely as phosphate shuttles,[10][4] while the dimeric Spo0B is catalytic; its phosphotransfer rate to the recipient response regulator is dramatically accelerated compared to histidine phosphate.[11] Despite possessing a second domain with some similarity to ATPase domains, dimeric HPt proteins have not been shown to bind or hydrolyze ATP and lack key residues present in other ATPases.[2]
The monomeric and dimeric forms do not have detectable
sequence similarity and are most likely not evolutionarily related; they are instead examples of convergent evolution.[2] Although dimeric HPts likely originate from degenerate histidine kinases, it is possible that monomeric HPts have a number of distinct origins, as there are few evolutionary constraints on the structure.[3]
Distribution
In
metazoans. Among known examples, most if not all eukaryotic two-component systems are hybrid kinase phosphorelays.[3]
A
filamentous fungi generally possessing more HPt proteins than yeasts; only one is encoded in the well-characterized Saccharomyces cerevisiae genome. Plants generally have more than one HPt, but fewer HPts than response regulators.[4][10]
References