Transcription Regulators in Archaea: Homologies and Differences with Bacterial Regulators.

The fitness and survival of prokaryotic microorganisms depends on their ability to adequately respond to environmental changes, sudden stress conditions and metabolic shifts. An important mechanism underlying this response is the regulation of gene expression mediated by transcription factors that are responsive to small-molecule ligands or other intracellular signals. Despite constituting a distinct domain of life from bacteria and harboring a eukaryotic-like basal transcription apparatus, it is well established that archaea have similar transcription factors pointing to the existence of shared ancestral proteins and to the occurrence of inter-domain horizontal gene transfer events. However, while global structural features of bacterial and archaeal transcription factors are indeed similar, other characteristics imply that archaeal regulators have undergone independent evolution. Here, we discuss the characteristics of Lrp/AsnC, MarR, ArsR/SmtB and TrmB families of transcription factors, which are the dominant families that constitute the transcription factor repertoire in archaea. We exemplify the evolutionary expansion of these families in archaeal lineages by emphasizing homologies and differences with bacterial counterparts in terms of ligand or signal response, physiological functions and mechanistic principles of regulation. As such, we aim to define future research approaches that enable further characterization of the functions and mechanisms of archaeal transcription factors.

A TetR-family transcription factor regulates fatty acid metabolism in the archaeal model organism Sulfolobus acidocaldarius.

Fatty acid metabolism and its regulation are known to play important roles in bacteria and eukaryotes. By contrast, although certain archaea appear to metabolize fatty acids, the regulation of the underlying pathways in these organisms remains unclear. Here, we show that a TetR-family transcriptional regulator (FadRSa) is involved in regulation of fatty acid metabolism in the crenarchaeon Sulfolobus acidocaldarius. Functional and structural analyses show that FadRSa binds to DNA at semi-palindromic recognition sites in two distinct stoichiometric binding modes depending on the operator sequence. Genome-wide transcriptomic and chromatin immunoprecipitation analyses demonstrate that the protein binds to only four genomic sites, acting as a repressor of a 30-kb gene cluster comprising 23 open reading frames encoding lipases and ß-oxidation enzymes. Fatty acyl-CoA molecules cause dissociation of FadRSa binding by inducing conformational changes in the protein. Our results indicate that, despite its similarity in overall structure to bacterial TetR-family FadR regulators, FadRSa displays a different acyl-CoA binding mode and a distinct regulatory mechanism.

Wing phosphorylation is a major functional determinant of the Lrs14-type biofilm and motility regulator AbfR1 in Sulfolobus acidocaldarius.

In response to a variety of environmental cues, prokaryotes can switch between a motile and a sessile, biofilm-forming mode of growth. The regulatory mechanisms and signaling pathways underlying this switch are largely unknown in archaea but involve small winged helix-turn-helix DNA-binding proteins of the archaea-specific Lrs14 family. Here, we study the Lrs14 member AbfR1 of Sulfolobus acidocaldarius. Small-angle X-ray scattering data are presented, which are consistent with a model of dimeric AbfR1 in which dimerization occurs via an antiparallel coiled coil as suggested by homology modeling. Furthermore, solution structure data of AbfR1-DNA complexes suggest that upon binding DNA, AbfR1 induces deformations in the DNA. The wing residues tyrosine 84 and serine 87, which are phosphorylated in vivo, are crucial to establish stable protein-DNA contacts and their substitution with a negatively charged glutamate or aspartate residue inhibits formation of a nucleoprotein complex. Furthermore, mutation abrogates the cellular abundance and transcription regulatory function of AbfR1 and thus affects the resulting biofilm and motility phenotype of S. acidocaldarius. This work establishes a novel wHTH DNA-binding mode for Lrs14-like proteins and hints at an important role for protein phosphorylation as a signal transduction mechanism for the control of biofilm formation and motility in archaea.