A Bioinformatics Analysis Reveals a Group of MocR Bacterial Transcriptional Regulators Linked to a Family of Genes Coding for Membrane Proteins.

Teresa Milano,Roberto Contestabile,Stefano Pascarella,Angela Tramonti,Martino Luigi Di Salvo,Sebastiana Angelaccio

doi:10.1155/2016/4360285

Abstract

The MocR bacterial transcriptional regulators are characterized by an N-terminal domain, 60 residues long on average, possessing the winged-helix-turn-helix (wHTH) architecture responsible for DNA recognition and binding, linked to a large C-terminal domain (350 residues on average) that is homologous to fold type-I pyridoxal 5′-phosphate (PLP) dependent enzymes like aspartate aminotransferase (AAT). These regulators are involved in the expression of genes taking part in several metabolic pathways directly or indirectly connected to PLP chemistry, many of which are still uncharacterized. A bioinformatics analysis is here reported that studied the features of a distinct group of MocR regulators predicted to be functionally linked to a family of homologous genes coding for integral membrane proteins of unknown function. This group occurs mainly in the Actinobacteria and Gammaproteobacteria phyla. An analysis of the multiple sequence alignments of their wHTH and AAT domains suggested the presence of specificity-determining positions (SDPs). Mapping of SDPs onto a homology model of the AAT domain hinted at possible structural/functional roles in effector recognition. Likewise, SDPs in wHTH domain suggested the basis of specificity of Transcription Factor Binding Site recognition. The results reported represent a framework for rational design of experiments and for bioinformatics analysis of other MocR subgroups.

Highlights

The members of the GntR family of bacterial transcriptional regulators are characterized by the presence of two domains [1]
Most regulons were from Actinobacteria; a few were found in Alpha- and Gammaproteobacteria (Table 1)
The sequences of the MocR proteins were multiply aligned along with those previously retrieved from RegPrecise databank. Both domains of the syntenic MocRs clustered in the same subtree. This pattern strongly supports the notion that the MocRs possibly involved in regulation of YczE genes share structural similarities that distinguish them from the other components of the same subfamily putatively involved in the regulation of other genes, such as those responsible for pyridoxal 5󸀠-phosphate (PLP) biosynthesis

Summary

Introduction

The members of the GntR family of bacterial transcriptional regulators are characterized by the presence of two domains [1]. The N-terminal domain, 60 residues long on average, displays the winged-helix-turn-helix (wHTH) architecture and is responsible for DNA recognition and binding [2]. The MocR [3, 4] subfamily of the GntR regulators (often denoted in the literature as GabR/MocR) is characterized by a large C-terminal domain (350 residues on average), whose structure is similar to fold type-I pyridoxal 5󸀠-phosphate (PLP) dependent enzymes [5]. The wHTH and AAT domains are connected to each other by a peptide linker of different lengths in different MocRs. The solution of the first threedimensional structure of a MocR, named GabR, from Bacillus subtilis [7, 8] confirmed the presence of a C-terminal fold type-I domain and provided fundamental insights for further investigations aimed at deciphering the mechanism of action of these regulators

Methods

Results

Discussion

Conclusion