|PROSITE documentation PDOC50894|
Most prokaryotic signal-transduction systems and a few eukaryotic pathways use phosphotransfer schemes involving two conserved components, a histidine protein kinase (HK) (see <PDOC50109>) and a response regulator protein (RR) (see <PDOC50110>). The HK, which is regulated by environmental stimuli, autophosphorylates at a histidine residue, creating a high-energy phosphoryl group that is subsequently transferred to an aspartate residue in the RR domain. Phosphorylation induces a conformational change in RR that results in activation of an associated domain that effects the response .
Besides these two signaling domains, a small number of two-component systems contain another common signaling domain, termed the Histidine-containing Phosphotransfer (HPt) domain. A large majority of prokaryotic HPt domains are part of multi-domain sensor kinases, whereas in eukaryotes they are found in separate independent proteins. HPt domains are ~120 amino acids in length and contain a histidine residue capable of participating in phosphoryl transfer reactions. They serve a dual purpose as a phosphoreceiver and phosphodonor in order to shuttle phosphoryl groups between two or more response regulator domains. The presence of HPt domains and use of multistep phosphorelay systems provide for additional points of regulation of signaling pathway .
The resolution of the 3D structure of some HPt domains revealed that they have a kidney shape and an all-α structure (see <PDB:1A0B>). Despite their overall low sequence homology and length variability, all of the HPts share a common up-down-up-down four-helix bundle core with the site of histidine phosphorylation located at the same position on the second helix. The most conserved positions are the phosphorylation site defined by the histidine followed by several highly conserved residues and a number of hydrophobic residues which seem to play a role in the formation of the hydrophobic core that allows association of the four-helix bundle [2,3,4,5].
The profile we developed covers the entire four-helix bundle core of the HPt domain.Last update:
February 2003 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Stock A.M. Robinson V.L. Goudreau P.N.|
|Title||Two-component signal transduction.|
|Source||Annu. Rev. Biochem. 69:183-215(2000).|
|2||Authors||Robinson V.L. Buckler D.R. Stock A.M.|
|Title||A tale of two components: a novel kinase and a regulatory switch.|
|Source||Nat. Struct. Biol. 7:626-633(2000).|
|3||Authors||Xu Q. West A.H.|
|Title||Conservation of structure and function among histidine-containing phosphotransfer (HPt) domains as revealed by the crystal structure of YPD1.|
|Source||J. Mol. Biol. 292:1039-1050(1999).|
|4||Authors||Kato M. Mizuno T. Shimizu T. Hakoshima T.|
|Title||Refined structure of the histidine-containing phosphotransfer (HPt) domain of the anaerobic sensor kinase ArcB from Escherichia coli at 1.57 A resolution.|
|Source||Acta Crystallogr. D 55:1842-1849(1999).|
|5||Authors||Ikegami T. Okada T. Ohki I. Hirayama J. Mizuno T. Shirakawa M.|
|Title||Solution structure and dynamic character of the histidine-containing phosphotransfer domain of anaerobic sensor kinase ArcB from Escherichia coli.|