A Radical Reimagining of Fungal Two-Component Regulatory Systems

Predicted Functional and Structural Diversity of Receiver Domains in Fungal Two-Component Regulatory Systems

“…Dashed lines indicate potential phosphotransfer reactions, based on our knowledge of bacterial TCSs. However, very few phosphotransfer reactions have been experimentally demonstrated in fungal TCSs outside S. cerevisiae , and there are good reasons to question whether most signaling pathways funnel through Ypd1 ( 9 ). Fungal HHKs are sorted into 19 groups (I to XIX) based on sequence differences, including various domains in the N-terminal regions.…”

“…Many fundamental features of fungal TCSs remain to be discovered. We have noted that published data cannot distinguish between two fundamental hypotheses, that all fungal HHKs participate in phosphorelays and that only HHKs regulating the high-osmolarity glycerol (HOG) stress response participate in phosphorelays ( 9 ). Here, we focused on fungal receiver domains.…”

“…In bacterial receiver domains, this often results in partial constitutive activity ( 17 ). We have previously proposed a possible mechanism by which a fungal HHK may activate Rim15 in Ascomycota ( 9 ).…”

“…We previously proposed that receiver domains of some fungal HHKs bind to protein targets other than Ypd1 ( 9 ). A potential mechanism is provided by the observation that 31% of the HHK receiver domains in our database contain insertions of 10 or more amino acids (relative to the length of the model bacterial receiver domain E. coli CheY) in the α2β3 and/or α3β4 loop ( Fig.…”

“…We can quantify this difference, as only 15% of fungal HHKs in our database are predicted to localize to the membrane. There are many theories about how cytoplasmic fungal HHKs might detect environmental stimuli ( 9 ) but few published experimental data. Fungal HHKs with transmembrane regions are concentrated in groups VI, XIII, XVI, XVII, XVIII, and XIX ( Fig.…”