Disease relevance of YPD1

• The C-terminal response regulator domains of SLN1 and SSK1 and full-length YPD1 have been overexpressed and purified from E. coli [1].

High impact information on YPD1

• Ypd1p binds to both Sln1p and Ssk1p and mediates the multistep phosphotransfer reaction (phosphorelay) [2].
• The yeast "two-component" osmotic stress phosphorelay consists of the histidine kinase, Sln1p, the phosphorelay intermediate, Ypd1p and two response regulators, Ssk1p and Skn7p, whose activities are regulated by phosphorylation of a conserved aspartyl residue in the receiver domain [3].
• The structure is composed of an up-down up-down four-helix bundle that is typical of histidine phosphotransfer or HPt domains such as Escherichia coli ArcB(C) and Saccharomyces cerevisiae Ypd1 [4].
• The histidine-containing phosphotransfer (HPt) protein YPD1 is an osmoregulatory protein in yeast that facilitates phosphoryl transfer between the two response regulator domains associated with SLN1 and SSK1 [5].
• The spy1(+) gene showed an ability to complement a mutational lesion of the Saccharomyces cerevisiae YPD1 gene, which is involved in an osmosensing signal transduction [6].

Biological context of YPD1

• In this comparative study, the molecular basis of interaction was examined between YPD1 and each of the three response regulator domains utilizing alanine scanning mutagenesis combined with a yeast two-hybrid assay [7].
• The results are consistent with a model in which the activated phenotype of the sln1* allele, sln-22, arises from a shift in the phosphotransfer equilibrium from Sln1p to Ypd1p, rather than from impaired dephosphorylation of the system in response to osmotic stress [8].
• Osmoregulation in Saccharomyces cerevisiae involves a multistep phosphorelay system requiring three proteins, SLN1, YPD1, and SSK1, that are related to bacterial two-component signaling proteins, in particular, those involved in regulating sporulation in Bacillus subtilis and anaerobic respiration in Escherichia coli [1].
• YPD1 has an open reading frame of 552 bp [9].
• It is located on chromosome 1 and an mRNA specific for YPD1 is detected under both yeast and hyphal growth [9].

Associations of YPD1 with chemical compounds

• Activation and control of the yeast HOG (High Osmolarity Glycerol) MAP kinase cascade is accomplished, in part, by a two-component sensory-response circuit comprised of the osmosensing histidine protein kinase Sln1p, the phospho-relay protein Ypd1p, and the response regulator protein Ssk1p [10].
• In addition, we have examined the roles of several conserved amino acid residues surrounding the phosphorylatable histidine (H64) of YPD1 using phosphoryl transfer reactions involving YPD1 mutants [11].
• The individual phosphoryl transfer reactions between YPD1 and the response regulator domains have been examined kinetically [11].
• The Sln1p aspartyl phosphate is then transferred to Ypd1p, which in turn transfers the phosphoryl group to a conserved aspartate on one of two response regulators, Ssk1p and Skn7p [8].
• Identification of YPD1, a gene of Candida albicans which encodes a two-component phosphohistidine intermediate protein [9].

Other interactions of YPD1

• This phosphate is then sequentially transferred to Sln1p-Asp-1144, then to Ypd1p-His64, and finally to Ssk1p-Asp554 [2].
• The SLN1-YPD1-SSK1 phosphorelay regulates a downstream mitogen-activated protein kinase cascade which ultimately controls the concentration of glycerol within the cell under hyperosmotic stress conditions [1].
• These observations suggest that Hik1 is a direct target of the fungicides or is a mediator of fungicide action and that the fungicidal effect is transmitted to the Hog1 pathway via Ypd1 [12].

Analytical, diagnostic and therapeutic context of YPD1

• Results from the yeast two-hybrid assay indicate that all three response regulator domains bind to a common area, largely hydrophobic in nature, on the surface of YPD1 [7].
• Based on the crystal structure of YPD1 and the sequence alignment of YPD1 with other HPt domains, we site-specifically engineered and purified several YPD1 mutants in order to examine the role of conserved residues surrounding the phosphorylatable histidine (H64) [5].
• Purification, crystallization and preliminary X-ray diffraction analysis of the yeast phosphorelay protein YPD1 [13].
• In Saccharomyces cerevisiae, a phosphorelay signal transduction pathway composed of Sln1p, Ypd1p, and Ssk1p, which are homologous to bacterial two-component signal transducers, is involved in the osmosensing mechanism [14].

References