Inter-domain signaling: clues and questions from the photoactive yellow protein family of photoreceptors

Photoactive yellow protein (PYP) is a bacterial photoreceptor protein that has served as a model system to study the biophysics of receptor activation. A next frontier is how the photoactivation of PYP causes a biological signal to be relayed to the next component in signal transduction chains. In general, the principles governing such inter-domain signal relay from an input protein to an output protein remain unclear. Two widely occurring evolutionary processes in Bacteria and Archaea can potentially provide insights into this question: (1) the two proteins involved in some cases are fused into one larger multi-domain protein; and (2) the genes encoding two proteins involved is some cases are encoded adjacent on the DNA in an operon. We cataloged these two processes for the PYP family of photoreceptors and used them to derive clues regarding inter-domain signaling mechanisms. Striking trends in the preference for which likely output domains are found in PYP multidomain proteins (and their C- versus N-terminal location) and which tentative output domains are present in pyp operons. The output domain preference of PYP also appears to be distinct from that for the related photoreceptor LOV. The mechanistic drivers of these differences remain unclear, but have implications for understanding biological signaling and for synthetic biology.