molecular biology Molecular biology is a branch of biology that seeks to understand the molecule, molecular basis of biological activity in and between Cell (biology), cells, including biomolecule, biomolecular synthesis, modification, mechanisms, and interactio ...

, the ferric uptake regulator family is a family of

bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

s involved in regulating

metal ion A metal () is a material that, when polished or fractured, shows a lustrous appearance, and conducts electricity and heat relatively well. These properties are all associated with having electrons available at the Fermi level, as against non ...

uptake and in metal

homeostasis In biology, homeostasis (British English, British also homoeostasis; ) is the state of steady internal physics, physical and chemistry, chemical conditions maintained by organism, living systems. This is the condition of optimal functioning fo ...

. The family is named for its founding member, known as the ferric uptake regulator or ferric uptake regulatory protein (Fur). Fur proteins are responsible for controlling the

intracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

concentration In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: '' mass concentration'', '' molar concentration'', '' number concentration'', ...

iron Iron is a chemical element; it has symbol Fe () and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, forming much of Earth's o ...

in many

. Iron is essential for most organisms, but its concentration must be carefully managed over a wide range of environmental conditions; high concentrations can be

toxic Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subst ...

due to the formation of

reactive oxygen species In chemistry and biology, reactive oxygen species (ROS) are highly Reactivity (chemistry), reactive chemicals formed from diatomic oxygen (), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (H2O2), superoxide (O2−), hydroxyl ...

Function

Members of the ferric uptake regulator family are

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...

s that primarily exert their regulatory effects as

repressor In molecular genetics, a repressor is a DNA- or RNA-binding protein that inhibits the expression of one or more genes by binding to the operator or associated silencers. A DNA-binding repressor blocks the attachment of RNA polymerase to the ...

s: when bound to their cognate metal ion, they are capable of binding

DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

and preventing expression of the genes they regulate, but under low concentrations of metal, they undergo a

conformational change In biochemistry, a conformational change is a change in the shape of a macromolecule, often induced by environmental factors. A macromolecule is usually flexible and dynamic. Its shape can change in response to changes in its environment or othe ...

that prevents DNA binding and lifts the repression. In the case of the ferric uptake regulator protein itself, its immediate downstream target is a

noncoding RNA A non-coding RNA (ncRNA) is a functional RNA molecule that is not translated into a protein. The DNA sequence from which a functional non-coding RNA is transcribed is often called an RNA gene. Abundant and functionally important types of non-co ...

called RyhB. The Ferric Uptake Regulator protein functions in Gram-negative and Gram-positive bacteria. Ferric uptake regulators act by sensing changes in free iron, so upon activation, they regulate target genes through interactions with the promoter region, known as the "Fur box". The magnetospirillum gryphiswaldense MSR-1 Fur is a key regulatory protein involved in maintaining iron homeostasis. This Fur is similar to the ''E. coli'' Fur, which acts by binding to Fur boxes to regulate gene expression as a way to maintain iron levels. Additionally, it serves as a model and foundation for other regulators that are able to sense changes in iron, zinc, and magnesium. In the image of the binding sites of magnetospirillum gryphiswaldense, the cyan color reflects the glutamate residues, while the magenta represents the histidine residues. These residues interact with the manganese ion to create binding site 1 in the ferric uptake regulator protein. In addition to the ferric uptake regulator protein, members of the Fur family are also involved in maintaining homeostasis with respect to other ions: * Mur, responsive to

manganese Manganese is a chemical element; it has Symbol (chemistry), symbol Mn and atomic number 25. It is a hard, brittle, silvery metal, often found in minerals in combination with iron. Manganese was first isolated in the 1770s. It is a transition m ...

. * Nur, responsive to

nickel Nickel is a chemical element; it has symbol Ni and atomic number 28. It is a silvery-white lustrous metal with a slight golden tinge. Nickel is a hard and ductile transition metal. Pure nickel is chemically reactive, but large pieces are slo ...

. *

PerR Perr may refer to: *Yechiel Perr (born 1935), American rabbi *Janet Perr, art director See also *George Samuel Perrottet (1793–1870), French botanist who used the botanical author abbreviation "Perr." *Per (disambiguation) *Purr (disambiguation ...

, responsive to

peroxide In chemistry, peroxides are a group of Chemical compound, compounds with the structure , where the R's represent a radical (a portion of a complete molecule; not necessarily a free radical) and O's are single oxygen atoms. Oxygen atoms are joined ...

; PerR monomers contain two binding sites and occur in zinc/iron and zinc/manganese forms. * Zur, responsive to

zinc Zinc is a chemical element; it has symbol Zn and atomic number 30. It is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodic tabl ...

; Zur regulates uptake and transport through a

regulon In molecular genetics, a regulon is a group of genes that are gene regulation, regulated as a unit, generally controlled by the same regulatory gene that gene expression, expresses a protein acting as a repressor or activator (genetics), activator ...

involving ZinT and the transporter ZnuABC. *Irr, responsive to iron through the status of

heme biosynthesis Heme (American English), or haem (Commonwealth English, both pronounced / hi:m/ ), is a ring-shaped iron-containing molecule that commonly serves as a ligand of various proteins, more notably as a component of hemoglobin, which is necessary to b ...

. Has both activator and repressor function. Prevalent in ''

Rhizobium ''Rhizobium'' is a genus of Gram-negative soil bacteria that fix nitrogen. ''Rhizobium'' species form an endosymbiotic nitrogen-fixing association with roots of (primarily) legumes and other flowering plants. The bacteria colonize plant ce ...

'', ''

Bradyrhizobium ''Bradyrhizobium'' is a genus of Gram-negative bacteria, Gram-negative soil bacteria, many of which fix nitrogen. Nitrogen fixation is an important part of the nitrogen cycle. Plants cannot use atmospheric nitrogen (N2); they must use nitrogen co ...

'' and many other

alphaproteobacteria ''Alphaproteobacteria'' or ''α-proteobacteria'', also called ''α-Purple bacteria'' in earlier literature, is a class of bacteria in the phylum '' Pseudomonadota'' (formerly "Proteobacteria"). The '' Magnetococcales'' and '' Mariprofundales'' ar ...

. The iron dependent repressor family is a functionally similar but non- homologous family of proteins involved in iron homeostasis in

prokaryote A prokaryote (; less commonly spelled procaryote) is a unicellular organism, single-celled organism whose cell (biology), cell lacks a cell nucleus, nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Ancient Gree ...

Relationship to virulence

Metal homeostasis can be a factor in bacterial

virulence Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most cases, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its abili ...

, an observation with a particularly long history in the case of iron. In some cases, expression of

virulence factor Virulence factors (preferably known as pathogenicity factors or effectors in botany) are cellular structures, molecules and regulatory systems that enable microbial pathogens (bacteria, viruses, fungi, and protozoa) to achieve the following: * c ...

s is under the regulatory control of the Fur protein.

References

{{InterPro content, IPR002481 Protein families