MOLECULAR BIOLOGY OF THE LysR FAMILY OF TRANSCRIPTIONAL REGULATORS

Abstract

The LysR family is composed of > 50 similar-sized, autoregulatory transcriptional regulators (LTTRs) that apparently evolved from a distant ancestor into subfamilies found in diverse prokaryotic genera. In response to different coinducers, LTTRs activate divergent transcription of linked target genes or unlinked regulons encoding extremely diverse functions. Mutational studies and amino acid sequence similarities of LTTRs identify: (a) a DNA-binding domain employing a helix-turn-helix motif (residues 1-65), (b) domains involved in coinducer recognition and/or response (residues 100-173 and 196-206), (c) a domain required for both DNA binding and coinducer response (residues 227-253). DNA footprinting studies suggest that in the absence of coinducer many LTTRs bind to regulated promoters via a 15-bp dyadic sequence with a common structure and position (near -65). Coinducer causes additional interactions of LTTRs with sequences near the -35 RNA polymerase binding site and/or DNA bending that results in transcription activation.

Common History at the Origin of the Position-Function Correlation in Transcriptional Regulators in Archaea and Bacteria

“…Members of the LysR family (Henikoff et al 1988;Schell 1993) were detected as a second group by the iterative search. This family has the DBD at the N terminus and two additional motifs that might be involved in metabolite recognition or in the multimerization process (Schell 1993).…”

“…This family has the DBD at the N terminus and two additional motifs that might be involved in metabolite recognition or in the multimerization process (Schell 1993). The importance of this second group is that it clearly separates the two classes of proteins with their HTH in the N terminus into the supergroup of negative regulators and the LysR family of dual regulators, or, more precisely, activators that repress their own expression.…”

Transcriptional organization of ThnI-regulated thienamycin biosynthetic genes in Streptomyces cattleya

“…Most studied LysR-type transcriptional activators interact with DNA boxes that contain the T-N 11 -A conserved motif sequence within an inverted repeat, usually in regions of overlapping divergent promoters that allow simultaneous bidirectional control of transcription. 19,20 Although several putative LysR T-N 11 -A boxes were found in the nucleotide sequence upstream of thnQ, thnH, thnP and thnK coding regions, additional studies are required to identify the binding sites for ThnI to exert its regulatory role. Regarding the autoregulatory nature of most characterized LysRtype transcriptional activators it should be mentioned that, although the 'classical' type of regulation is by transcriptional activation and negative autoregulation, 20 there is an increasing body of knowledge indicating that an additional class of LysR-type regulators, acting as transcriptional activators or repressors, is subjected to positive autoregulation.…”

“…19,20 Although several putative LysR T-N 11 -A boxes were found in the nucleotide sequence upstream of thnQ, thnH, thnP and thnK coding regions, additional studies are required to identify the binding sites for ThnI to exert its regulatory role. Regarding the autoregulatory nature of most characterized LysRtype transcriptional activators it should be mentioned that, although the 'classical' type of regulation is by transcriptional activation and negative autoregulation, 20 there is an increasing body of knowledge indicating that an additional class of LysR-type regulators, acting as transcriptional activators or repressors, is subjected to positive autoregulation. 19 The data presented here suggest that ThnI belongs to this class of positively autoregulatory activators of the LysR family.…”

Rhodococcus equi

“…LTTR are, after the two component response regulators, the second largest class of bacterial regulatory proteins [61]. The more than 100 proteins assigned to this family control a wide range of bacterial processes, for example bacterial carbon dioxide fixation (CbbR) and oxygen stress response in pathogens (OxyR).…”