Dataset Information

Metalloregulatory proteins: metal selectivity and allosteric switching.

ABSTRACT: Prokaryotic organisms have evolved the capacity to quickly adapt to a changing and challenging microenvironment in which the availability of both biologically required and non-essential transition metal ions can vary dramatically. In all bacteria, a panel of metalloregulatory proteins controls the expression of genes encoding membrane transporters and metal trafficking proteins that collectively manage metal homeostasis and resistance. These "metal sensors" are specialized allosteric proteins, in which the direct binding of a specific or small number of "cognate" metal ion(s) drives a conformational change in the regulator that allosterically activates or inhibits operator DNA binding, or alternatively, distorts the promoter structure thereby converting a poor promoter to a strong one. In this review, we discuss our current understanding of the features that control metal specificity of the allosteric response in these systems, and the role that structure, thermodynamics and conformational dynamics play in mediating allosteric activation or inhibition of DNA binding.

SUBMITTER: Reyes-Caballero H

PROVIDER: S-EPMC3097251 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Metalloregulatory proteins: metal selectivity and allosteric switching.

Reyes-Caballero Hermes H Campanello Gregory C GC Giedroc David P DP

Biophysical chemistry 20110405 2-3

Prokaryotic organisms have evolved the capacity to quickly adapt to a changing and challenging microenvironment in which the availability of both biologically required and non-essential transition metal ions can vary dramatically. In all bacteria, a panel of metalloregulatory proteins controls the expression of genes encoding membrane transporters and metal trafficking proteins that collectively manage metal homeostasis and resistance. These "metal sensors" are specialized allosteric proteins, i ...[more]

PMID: 21511390

Similar Datasets

Project description:Streptococcus mutans is the causative agent of dental caries, a significant concern for human health, and therefore an attractive target for therapeutics development. Previous work in our laboratory has identified a homodimeric, manganese-dependent repressor protein, SloR, as an important regulator of cariogenesis and has used site-directed mutagenesis to map functions to specific regions of the protein. Here we extend those studies to better understand the structural interaction between SloR and its operator and its effector metal ions. The results of DNase I assays indicate that SloR protects a 42-bp region of DNA that overlaps the sloABC promoter on the S. mutans UA159 chromosome, while electrophoretic mobility shift and solution binding assays indicate that each of two SloR dimers binds to this region. Real-time semiquantitative reverse transcriptase PCR (real-time semi-qRT-PCR) experiments were used to determine the individual base pairs that contribute to SloR-DNA binding specificity. Solution studies indicate that Mn(2+) is better than Zn(2+) at specifically activating SloR to bind DNA, and yet the 2.8-Å resolved crystal structure of SloR bound to Zn(2+) provides insight into the means by which selective activation by Mn(2+) may be achieved and into how SloR may form specific interactions with its operator. Taken together, these experimental observations are significant because they can inform rational drug design aimed at alleviating and/or preventing S. mutans-induced caries formation.This report focuses on investigating the SloR protein as a regulator of essential metal ion transport and virulence gene expression in the oral pathogen Streptococcus mutans and on revealing the details of SloR binding to its metal ion effectors and binding to DNA that together facilitate this expression. We used molecular and biochemical approaches to characterize the interaction of SloR with Mn(2+) and with its SloR recognition element to gain a clearer picture of the regulatory networks that optimize SloR-mediated metal ion homeostasis and virulence gene expression in S. mutans. These experiments can have a significant impact on caries treatment and/or prevention by revealing the S. mutans SloR-DNA binding interface as an appropriate target for the development of novel therapeutic interventions.

Dataset Information

Metalloregulatory proteins: metal selectivity and allosteric switching.

Publications

Metalloregulatory proteins: metal selectivity and allosteric switching.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets