The West group is interested in elucidating the role of phosphorylation and dephosphorylation in regulating protein function within the yeast His-Asp phosphorelay signaling pathway. The relative simplicity of the yeast system (one HK, one HPt and two RRs) together with our recent X-ray crystallographic studies of the YPD1 HPt protein in complex with the SLN1 receiver domain, provides an excellent foundation for the investigation of molecular interactions within this phosphorelay signaling system. Our long term objectives are to achieve a detailed understanding of the structural, biochemical and functional implications of YPD1 interactions with the three homologous response regulator domains associated with SLN1, SSK1 and SKN7.
Signal Transduction in Yeast
Branched multi-step His-Asp phosphorelay signaling pathways are central to the ability of fungal cells to respond to environmental stress. In yeast, S. cerevisiae, the histidine-containing phosphotransfer (HPt) protein YPD1 is required for phosphoryl group transfer from SLN1, a membrane-bound sensor histidine kinase (HK) to two response regulator (RR) proteins (SSK1 in the cytoplasm and SKN7 in the nucleus), which mediate osmotic and cell wall stress responses. In fungal pathogens, His-Asp phosphorelay signaling pathways are widely implicated in pathogenesis and, because they are unique to lower eukaryotes and plants, these pathways are excellent targets for antifungal drug development.
Molecular surface representation of the phosphorelay protein YPD1
The West group is also engaged in a collaborative project related to anaerobic structural biology as part of the Price Family Foundation Institute of Structural Biology (see OU Press Release dated Jan. 24, 2014).