SSF47226

Histidine-containing phosphotransfer domain, HPT domain

SUPERFAMILY entry
Member databaseSUPERFAMILY
SUPERFAMILY typehomologous superfamily

Description
Imported from IPR036641

This superfamily represents a domain present at the N terminus in proteins which undergo autophosphorylation. The group includes histidine kinases such as CheA from Escherichia coli, the gliding motility regulatory protein from Myxococcus xanthus, and a number of bacterial chemotaxis proteins.

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
[10, 11]
. Examples of histidine kinases are EnvZ, which plays a central role in osmoregulation
[8]
, and CheA, which plays a central role in the chemotaxis system
[9]
. 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
[1]
. The kinase core has a unique fold, distinct from that of the Ser/Thr/Tyr kinase superfamily.

Two-component signal transduction systems enable bacteria to sense, respond, and adapt to a wide range of environments, stressors, and growth conditions
[6]
. Some bacteria can contain up to as many as 200 two-component systems that need tight regulation to prevent unwanted cross-talk
[5]
. 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
[7]
. Two-component systems are comprised of a sensor histidine kinase (HK) and its cognate response regulator (RR)
[2]
. 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
[4, 3]
.

References
Imported from IPR036641

1.Bacteriophytochromes: new tools for understanding phytochrome signal transduction. Vierstra RD, Davis SJ. Semin. Cell Dev. Biol. 11, 511-21, (2000). View articlePMID: 11145881

2.Two-component signal transduction. Stock AM, Robinson VL, Goudreau PN. Annu. Rev. Biochem. 69, 183-215, (2000). View articlePMID: 10966457

3.Keeping signals straight in phosphorelay signal transduction. Hoch JA, Varughese KI. J. Bacteriol. 183, 4941-9, (2001). View articlePMID: 11489844

4.Molecular recognition of bacterial phosphorelay proteins. Varughese KI. Curr. Opin. Microbiol. 5, 142-8, (2002). View articlePMID: 11934609

5.Specificity in two-component signal transduction pathways. Laub MT, Goulian M. Annu. Rev. Genet. 41, 121-45, (2007). View articlePMID: 18076326

6.Two-component signal transduction pathways regulating growth and cell cycle progression in a bacterium: a system-level analysis. Skerker JM, Prasol MS, Perchuk BS, Biondi EG, Laub MT. PLoS Biol. 3, e334, (2005). View articlePMID: 16176121

7.Histidine protein kinases: key signal transducers outside the animal kingdom. Wolanin PM, Thomason PA, Stock JB. Genome Biol. 3, REVIEWS3013, (2002). View articlePMID: 12372152

8.Solution structure of the homodimeric core domain of Escherichia coli histidine kinase EnvZ. Tomomori C, Tanaka T, Dutta R, Park H, Saha SK, Zhu Y, Ishima R, Liu D, Tong KI, Kurokawa H, Qian H, Inouye M, Ikura M. Nat. Struct. Biol. 6, 729-34, (1999). View articlePMID: 10426948

9.Structure of CheA, a signal-transducing histidine kinase. Bilwes AM, Alex LA, Crane BR, Simon MI. Cell 96, 131-41, (1999). View articlePMID: 9989504

10.Protein aspartate phosphatases control the output of two-component signal transduction systems. Perego M, Hoch JA. Trends Genet. 12, 97-101, (1996). View articlePMID: 8868347

11.Histidine kinases and response regulator proteins in two-component signaling systems. West AH, Stock AM. Trends Biochem. Sci. 26, 369-76, (2001). View articlePMID: 11406410

Further reading

12. Communication modules in bacterial signaling proteins. Parkinson JS, Kofoid EC. Annu. Rev. Genet. 26, 71-112, (1992). View articlePMID: 1482126

13. Protein histidine kinases and signal transduction in prokaryotes and eukaryotes. Alex LA, Simon MI. Trends Genet. 10, 133-8, (1994). View articlePMID: 8029829

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