Fatty acid metabolism regulator protein FadR
Encyclopedia
In molecular biology, the fatty acid metabolism regulator protein FadR, is a bacterial transcription factor
.
Bacteria regulate membrane
fluidity by manipulating the relative levels of saturated and unsaturated fatty acids within the phospholipid
s of their membrane bilayers. In Escherichia coli
, the transcription factor, FadR, functions as a switch that co-ordinately regulates
the machinery required for fatty acid
beta-oxidation and the expression
of a key enzyme
in fatty acid biosynthesis. This single [repressor controls the transcription of the whole fad regulon. Binding of fadR is specifically inhibited by long chain fatty acyl-CoA
compounds.
The crystal structure
of FadR reveals a two domain
dimeric
molecule
where the N-terminal winged-helix domain
binds DNA
, and the C-terminal domain binds acyl-CoA. The binding of acyl-CoA to the C-terminal domain results in a conformational change
that affects the DNA binding affinity of the N-terminal domain.
FadR is a member of the GntR family
of bacterial
transcription regulator
s. The DNA-binding domain is well conserved
for this family, whereas the C-terminal effector-binding domain is more variable, and is consequently used to define the GntR subfamilies. The FadR group is the largest subgroup, and is characterised by an all-helical C-terminal domain composed of 6 to 7 alpha helices
.
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
.
Bacteria regulate membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
fluidity by manipulating the relative levels of saturated and unsaturated fatty acids within the phospholipid
Phospholipid
Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from...
s of their membrane bilayers. In Escherichia coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
, the transcription factor, FadR, functions as a switch that co-ordinately regulates
Regulation of gene expression
Gene modulation redirects here. For information on therapeutic regulation of gene expression, see therapeutic gene modulation.Regulation of gene expression includes the processes that cells and viruses use to regulate the way that the information in genes is turned into gene products...
the machinery required for fatty acid
Fatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
beta-oxidation and the expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
of a key enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
in fatty acid biosynthesis. This single [repressor controls the transcription of the whole fad regulon. Binding of fadR is specifically inhibited by long chain fatty acyl-CoA
Acyl-CoA
Acyl-CoA is a group of coenzymes involved in the metabolism of fatty acids. It is a temporary compound formed when coenzyme A attaches to the end of a long-chain fatty acid inside living cells. The compound undergoes beta oxidation, forming one or more molecules of acetyl-CoA...
compounds.
The crystal structure
Crystal structure
In mineralogy and crystallography, crystal structure is a unique arrangement of atoms or molecules in a crystalline liquid or solid. A crystal structure is composed of a pattern, a set of atoms arranged in a particular way, and a lattice exhibiting long-range order and symmetry...
of FadR reveals a two domain
Protein domain
A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...
dimeric
Protein dimer
In biochemistry, a dimer is a macromolecular complex formed by two, usually non-covalently bound, macromolecules like proteins or nucleic acids...
molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
where the N-terminal winged-helix domain
Winged-helix transcription factors
Consisting of about 110 amino acids, the domain in winged-helix transcription factors has four helices and a two-strand beta-sheet.These proteins are classified into 17 families called FoxA-FoxQ....
binds DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
, and the C-terminal domain binds acyl-CoA. The binding of acyl-CoA to the C-terminal domain results in a conformational change
Conformational change
A macromolecule is usually flexible and dynamic. It can change its shape in response to changes in its environment or other factors; each possible shape is called a conformation, and a transition between them is called a conformational change...
that affects the DNA binding affinity of the N-terminal domain.
FadR is a member of the GntR family
GntR-like bacterial transcription factors
In molecular biology, the GntR-like bacterial transcription factors are a family of transcription factors.Many bacterial transcription regulation proteins bind DNA through a helix-turn-helix motif, which can be classified into subfamilies on the basis of sequence similarities...
of bacterial
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
transcription regulator
Transcriptional regulation
Transcriptional regulation is the change in gene expression levels by altering transcription rates. -Regulation of transcription:Regulation of transcription controls when transcription occurs and how much RNA is created...
s. The DNA-binding domain is well conserved
Conserved sequence
In biology, conserved sequences are similar or identical sequences that occur within nucleic acid sequences , protein sequences, protein structures or polymeric carbohydrates across species or within different molecules produced by the same organism...
for this family, whereas the C-terminal effector-binding domain is more variable, and is consequently used to define the GntR subfamilies. The FadR group is the largest subgroup, and is characterised by an all-helical C-terminal domain composed of 6 to 7 alpha helices
Alpha helix
A common motif in the secondary structure of proteins, the alpha helix is a right-handed coiled or spiral conformation, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier...
.