Structural insights into the function of the core-circadian factor TIMING OF CAB2 EXPRESSION 1 (TOC1)

BACKGROUND: The plant circadian clock has at its core a feedback loop that includes TIMING OF CAB2 EXPRESSION 1 (TOC1). This protein has an as of yet unknown biochemical activity. It has been noted that the extreme amino-terminus of this protein is distantly related in sequence to response regulators (RR), and thus TOC1 is a member of the so-called pseudo response regulator (PRR) family. As well, the extreme carboxy-terminus has a small sequence stretch related to the other PRRs and CONSTANS (CO)-like proteins, and this peptide stretch has been termed the CCT (for CONSTANS, CONSTANS-LIKE, TOC1) domain. METHODS: To extend further our understanding of the TOC1 protein, we performed a ROSETTA structural prediction on TOC1 orthologues from four plant species. Phylogenetic interpretations assisted in model construction. RESULTS: From our models, we suggest that TOC1 is a three-domain protein: TOC1 has an amino-terminal signaling-domain related to response receivers, a carboxy-terminal domain that could participate both in metal binding and in transcriptional regulation, and a linker domain that connects the two. CONCLUSION: The models we present should prove useful in future hypothesis-driven biochemical analyses to test the predictions that TOC1 is a multi-domain signaling component of the plant circadian clock.