Crystal structure of the Lrp-like transcriptional regulator from the archaeon Pyrococcus furiosus

The LrpA protein from the hyperthermophilic archaeon Pyrococcusfuriosus bel ongs to the Lrp/AsnC family of transcriptional regulatory proteins, of whic h the Escherichia coli leucine-responsive regulatory protein is the archety pe. Its crystal structure has been determined at 2.9 Angstrom resolution an d is the first for a member of the Lrp/AsnC family, as well as one of the f irst for a transcriptional regulator from a hyperthermophile. The structure consists of an N-terminal domain containing a helix-turn-helix (HtH) DNA-b inding motif, and a C-terminal domain of mixed alpha/beta character reminis cent of a number of RNA- and DNA-binding domains. Pyrococcus furiosus LrpA forms a homodimer mainly through interactions between the antiparallel beta -sheets of the C-terminal domain, and further interactions lead to octamer formation. The LrpA structure suggests how the protein might bind and poss ibly distort its DNA substrate through use of its HtH motifs and control ge ne expression. A possible location for an effector binding site is proposed by using sequence comparisons with other members of the family coupled to mutational analysis.