Insights into eukaryotic multistep phosphorelay signal transduction revealed by the crystal structure of Ypd1p from Saccharomyces cerevisiae

"Two-component" phosphorelay signal transduction systems constitute a poten tial target for antibacterial and antifungal agents, since they are found e xclusively in prokaryotes and lower eukaryotes (yeast, fungi, slime mold, a nd plants) but not in mammalian organisms. Saccharomyces cerevisiae Ypd1p, a key intermediate in the osmosensing multistep phosphorelay signal transdu ction, catalyzes the phosphoryl group transfer between response regulators. Its 1.8 Angstrom structure, representing the first example of a eukaryotic phosphorelay protein, contains a four-helix bundle as in the HPt domain of Escherichia coli ArcB sensor kinase. However, Ypd1p has a 44-residue inser tion between the last two helices of the helix bundle. The side-chain of Hi s64, the site of phosphorylation, protrudes into the solvent. The structura l resemblance between Ypd1p and ArcB HPt domain suggests that both prokaryo tes and lower eukaryotes utilize the same basic protein fold for phosphorel ay signal transduction. This study sheds light on the best characterized eu karyotic phosphorelay system. (C) 1999 Academic Press.