Metalloregulatory proteins: Metal selectivity and allosteric switching

Abstract

Prokaryotic organisms have evolved an impressive 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 control 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.

Bacterial Strategies to Maintain Zinc Metallostasis at the Host-Pathogen Interface

“…This model is dictated by the sensitivity (K metal ) of the metalloregulatory or metal sensor protein, which transcriptionally regulates the expression of genes that encode metal transporters and other resistance proteins (17)(18)(19) (Fig. 2).…”

The Zinc-Responsive Regulon of Neisseria meningitidis Comprises 17 Genes under Control of a Zur Element

“…On the one hand, bacteria have to cope with decreased zinc availability during infection in the host (25), while on the other, at high concentrations, zinc can lead to the production of toxic reactive oxygen species (49). Hence, bacteria tightly control metal homeostasis by metalloregulatory proteins, which are specialized metal-sensing transcriptional regulators that change their conformation upon binding of the metal ions (5).…”

Metal Transport in the Rhizobium-Legume Symbiosis

“…These systems include a number of metal transporter families, several types of organic molecules that can bind metals with high affi nity, soluble proteins that shuttle metal in the cytosol (metallochaperones) or that simply bind excess metals (metallothioneins), and transcription factors that regulate the process (Wandersman and Delepelaire 2004, Waldron and Robinson 2009, Blindauer and Leszczyszyn 2010, Reyes-Caballero et al 2011, Argüello et al 2012. Overall, the mechanisms governing metal homeostasis are so effi cient that the "free", hydrated, cytosolic metal concentration of a typical bacteria is in the pMfM range (Outten and O'Halloran 2001), which is less than one free ion per cell.…”