Structure and function of the feast/famine regulatory proteins, FFRPs

Abstract

Feast/famine regulatory proteins (FFRPs) include a diverse family of transcription factors of archaea and eubacteria. The best characterized among FFRPs is E. coli Lrp (the leucine-responsive regulatory protein). A full length FFRP is composed of an N-terminal DNA-binding domain and a C-terminal assembly domain. The C-domain is involved in formation of a dimer, and higher structures (e.g. a disk composed of 4 dimers, a chromatin-like cylinder) are further assembled. A pair of DNA-binding domains in an FFRP dimer bind the DNA site NANBNCNDNETTTN ENDNCNBNA, where N A and NA, e.g., are bases complementary to each other, and NE is either A or T. Such 13 bp sequences repeat with insertions of 7-8 or ∼18 basepairs in promoters regulated by FFRPs. Ligands of the size of amino acids (e.g. leucine, asparagine) signal metabolic or environmental changes directly to FFRPs by binding at the interface formed between dimers. This interaction alters the assembly form, and thus the overall DNA-binding specificity. In this way, Lrp regulates a large number of genes differently in E. coli. In Pyrococcus sp. OT3, 14 FFRPs possibly regulate many of the ∼1,500 genes coded. It is widely believed that the common ancestor of all organisms first differentiated to archaea and eubacteria. Thus, global (i.e. genome wide) regulation by FFRPs can be the prototype of highly differentiated transcription regulatory systems found in organisms nowadays.