An update of the unceasingly growing and diverse AraC/XylS family of transcriptional activators

Abstract

Transcriptional factors play an important role in gene regulation in all organisms, especially in Bacteria. Here special emphasis is placed in the AraC/XylS family of transcriptional regulators. This is one of the most abundant as many predicted members have been identified and more members are added because more bacterial genomes are sequenced. Given the way more experimental evidence has mounded in the past decades, we decided to update the information about this captivating family of proteins. Using bioinformatics tools on all the data available for experimentally characterized members of this family, we found that many members that display a similar functional classification can be clustered together and in some cases they have a similar regulatory scheme. A proposal for grouping these proteins is also discussed. Additionally, an analysis of surveyed proteins in bacterial genomes is presented. Altogether, the current review presents a panoramic view into this family and we hope it helps to stimulate future research in the field.

Optimised Heterologous Expression and Functional Analysis of the Yersinia pestis F1-Capsular Antigen Regulator Caf1R

“…Yersinia pestis F1-capsule regulator (activator), Caf1R, is a member of the widely distributed A/X family of the bacterial transcription factors/regulators. Regulators belonging to this family are found in >80% of non-redundant prokaryote genomes and are involved in regulating genes essential in central metabolism, stress-response and virulence [19]. A great number of proteins in this family are notoriously difficult to purify in their native functional state.…”

“…Expression from the caf locus is controlled by a transcriptional activator known as Caf1R [18]. Caf1R belongs to the AraC/XylS (A/X) family of bacterial transcriptional regulators [19,20]. Regulators belonging to the A/X family are widespread among both Gram-negative and Gram-positive bacteria, spanning >80% of the 'non-redundant' prokaryote genomes [21].…”

“…They control expression of genes involved in diverse biological processes from metabolism to stress responses and virulence, as reviewed by Cortes-Avalos et al [19,20]. Proteins of this family are characterised by a signatory DNA-binding domain (DBD) of~100 amino acids, often located at the C-terminus, accompanied by a sensing or oligomerisation domain of~100-200 amino acids that could be located at either end, N-or C-terminus.…”

“…A few regulators of this family possess only the signatory DBD, such as MarA and its homologue, SoxS [22]. The signatory DBD contains a conserved tertiary structure composed of 7 α-helices and binds to the promoter/operator region of target operon(s) via two Helixturn-Helix (HTH) motifs, connected by a central α-helix or turn [19,23]. The A/X family regulators often activate expression although some such as AraC may act as both activator and repressor [19,20].…”

“…Bacterial regulators are generally expressed at low levels in the cell and many proteins of this family when overexpressed, tend to form 'inactive' aggregates also known as inclusion bodies. This is a likely explanation why only a small number (n = 126), have been characterised experimentally so far [19], as it is therefore inherently difficult to purify A/X family members in the soluble 'active' form. MarA and Rob are the only two proteins of A/X family whose high-resolution crystal structures have been deduced with their cognate promoter DNA ligands [24,25].…”