In multistep phosphorelay (MSP) pathway, the His-containing phosphotransmitters encoded by AHP genes in Arabidopsis act as signaling intermediates integrating signaling inputs from diverse sensor histidine kinases In comparison to prototypical two-component signaling in bacteria displaying high level of specificity, the level of specificity in related plant MSP signaling remained unclear Here I will describe our results employing both experimental and computational approaches in the identification of structural determinants of specificity in MSP signaling in Arabidopsis