DNA-binding protein
Encyclopedia
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s that are composed of DNA-binding domain
DNA-binding domain
A DNA-binding domain is an independently folded protein domain that contains at least one motif that recognizes double- or single-stranded DNA. A DBD can recognize a specific DNA sequence or have a general affinity to DNA...
s and thus have a specific or general affinity for either single or double stranded 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...
. Sequence-specific DNA-binding proteins generally interact with the major groove of B-DNA, because it exposes more functional group
Functional group
In organic chemistry, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part of...
s that identify a base pair
Base pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...
. However there are some known minor groove DNA-binding ligands such as Netropsin
Netropsin
Netropsin is an oligopeptide with antibiotic and antiviral activity.Netropsin was discovered by Finlay et al. and first isolated from the actinobacterium Streptomyces netropsis. It belongs to the class of pyrrole-amidine antibiotics...
, Distamycin, Hoechst 33258, Pentamidine
Pentamidine
Pentamidine is an antimicrobial medication given for prevention and treatment of Pneumocystis pneumonia caused by Pneumocystis jirovecii , a severe interstitial type of pneumonia often seen in patients with HIV infection...
and others.
Examples
DNA-binding proteinProtein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s include transcription factors which modulate the process of transcription, various polymerases, nucleases which cleave DNA molecules, and histones which are involved in chromosome packaging in the cell nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
. DNA-binding proteins can incorporate such domains as the zinc finger
Zinc finger
Zinc fingers are small protein structural motifs that can coordinate one or more zinc ions to help stabilize their folds. They can be classified into several different structural families and typically function as interaction modules that bind DNA, RNA, proteins, or small molecules...
, the helix-turn-helix
Helix-turn-helix
In proteins, the helix-turn-helix is a major structural motif capable of binding DNA. It is composed of two α helices joined by a short strand of amino acids and is found in many proteins that regulate gene expression...
, and the leucine zipper
Leucine zipper
A leucine zipper, aka leucine scissors, is a common three-dimensional structural motif in proteins. These motifs are usually found as part of a DNA-binding domain in various transcription factors, and are therefore involved in regulating gene expression...
(among many others) that facilitate binding to nucleic acid.
Non-specific DNA-protein interactions
Structural proteins that bind DNA are well-understood examples of non-specific DNA-protein interactions. Within chromosomes, DNA is held in complexes with structural proteins. These proteins organize the DNA into a compact structure called chromatinChromatin
Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...
. In eukaryotes this structure involves DNA binding to a complex of small basic proteins called histone
Histone
In biology, histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. They are the chief protein components of chromatin, acting as spools around which DNA winds, and play a role in gene regulation...
s, while in prokaryotes multiple types of proteins are involved. The histones form a disk-shaped complex called a nucleosome
Nucleosome
Nucleosomes are the basic unit of DNA packaging in eukaryotes, consisting of a segment of DNA wound around a histone protein core. This structure is often compared to thread wrapped around a spool....
, which contains two complete turns of double-stranded DNA wrapped around its surface. These non-specific interactions are formed through basic residues in the histones making ionic bond
Ionic bond
An ionic bond is a type of chemical bond formed through an electrostatic attraction between two oppositely charged ions. Ionic bonds are formed between a cation, which is usually a metal, and an anion, which is usually a nonmetal. Pure ionic bonding cannot exist: all ionic compounds have some...
s to the acidic sugar-phosphate backbone of the DNA, and are therefore largely independent of the base sequence. Chemical modifications of these basic amino acid residues include methylation
Methylation
In the chemical sciences, methylation denotes the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. Methylation is a form of alkylation with, to be specific, a methyl group, rather than a larger carbon chain, replacing a hydrogen atom...
, phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
and acetylation
Acetylation
Acetylation describes a reaction that introduces an acetyl functional group into a chemical compound...
. These chemical changes alter the strength of the interaction between the DNA and the histones, making the DNA more or less accessible to transcription factor
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...
s and changing the rate of transcription. Other non-specific DNA-binding proteins in chromatin include the high-mobility group proteins, which bind to bent or distorted DNA. These proteins are important in bending arrays of nucleosomes and arranging them into the larger structures that make up chromosomes.
DNA-binding proteins that specifically bind single-stranded DNA
A distinct group of DNA-binding proteins are the DNA-binding proteins that specifically bind single-stranded DNA. In humans, replication protein AReplication protein A
Replication protein A is a protein that binds single-stranded DNA in eukaryotic cells. During DNA replication, RPA prevents single-stranded DNA from winding back on itself or from forming secondary structures. This keeps DNA unwound for the polymerase to replicate it...
is the best-understood member of this family and is used in processes where the double helix is separated, including DNA replication, recombination and DNA repair. These binding proteins seem to stabilize single-stranded DNA and protect it from forming stem-loop
Stem-loop
Stem-loop intramolecular base pairing is a pattern that can occur in single-stranded DNA or, more commonly, in RNA. The structure is also known as a hairpin or hairpin loop. It occurs when two regions of the same strand, usually complementary in nucleotide sequence when read in opposite directions,...
s or being degraded by nuclease
Nuclease
A nuclease is an enzyme capable of cleaving the phosphodiester bonds between the nucleotide subunits of nucleic acids. Older publications may use terms such as "polynucleotidase" or "nucleodepolymerase"....
s.
Binding to particular DNA sequences
In contrast, other proteins have evolved to bind to particular DNA sequences. The most intensively studied of these are the various transcription factorTranscription 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...
s, which are proteins that regulate transcription. Each transcription factor binds to one particular set of DNA sequences and activates or inhibits the transcription of genes that have these sequences close to their promoters. The transcription factors do this in two ways. Firstly, they can bind the RNA polymerase responsible for transcription, either directly or through other mediator proteins; this locates the polymerase at the promoter and allows it to begin transcription. Alternatively, transcription factors can bind 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...
s that modify the histones at the promoter; this will change the accessibility of the DNA template to the polymerase.
As these DNA targets can occur throughout an organism's genome, changes in the activity of one type of transcription factor can affect thousands of genes. Consequently, these proteins are often the targets of the signal transduction
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
processes that control responses to environmental changes or cellular differentiation
Cellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...
and development. The specificity of these transcription factors' interactions with DNA come from the proteins making multiple contacts to the edges of the DNA bases, allowing them to "read" the DNA sequence. Most of these base-interactions are made in the major groove, where the bases are most accessible. Mathematical descriptions of protein-DNA binding taking into account sequence-specificity, competitive and cooperative binding of proteins of different types are usually performed with the help of the lattice models.
See also
- DNA-binding domainDNA-binding domainA DNA-binding domain is an independently folded protein domain that contains at least one motif that recognizes double- or single-stranded DNA. A DBD can recognize a specific DNA sequence or have a general affinity to DNA...
- Single-strand binding proteinSingle-strand binding proteinSingle-strand binding protein, also known as SSB or SSBP, binds to single stranded regions of DNA to prevent premature annealing. The strands have a natural tendency to revert to the duplex form, but SSB binds to the single strands, keeping them separate and allowing the DNA replication machinery...
- Zinc fingerZinc fingerZinc fingers are small protein structural motifs that can coordinate one or more zinc ions to help stabilize their folds. They can be classified into several different structural families and typically function as interaction modules that bind DNA, RNA, proteins, or small molecules...
- Leucine ZipperLeucine zipperA leucine zipper, aka leucine scissors, is a common three-dimensional structural motif in proteins. These motifs are usually found as part of a DNA-binding domain in various transcription factors, and are therefore involved in regulating gene expression...
- bZIP domainBZIP domainThe Basic Leucine Zipper Domain is found in many DNA binding eukaryotic proteins. One part of the domain contains a region that mediates sequence specific DNA binding properties and the leucine zipper that is required for the dimerization of two DNA binding regions. The DNA binding region...
- Helix-turn-helixHelix-turn-helixIn proteins, the helix-turn-helix is a major structural motif capable of binding DNA. It is composed of two α helices joined by a short strand of amino acids and is found in many proteins that regulate gene expression...
- Helix-loop-helix
- HMG-boxHMG-boxThe HMG-box is a protein domain which is involved in DNA binding.-Structure:The structure of the HMG-box domain contains three alpha helices separated by loops .-Function:...
- LexitropsinLexitropsinLexitropsins is a family of semi-synthetic DNA-binding ligands.They are analogs of natural antibiotics Netropsin and Distamycin. Antibiotics of this group are capable to bind with a narrow groove of DNA with different sequence-selectivity. Lexitropsins form a complexes with DNA with stoichiometry...
- Nucleic acid simulations
External links
- Abalone tool for modeling DNA-ligand interactions.
- DBD database of predicted transcription factors Uses a curated set of DNA-binding domains to predict transcription factors in all completely sequenced genomes