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The TATA-binding protein (TBP) is a general transcription factor that binds to a
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 ...
sequence called the TATA box. This DNA sequence is found about 30
base pair A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
s upstream of the
transcription start site Transcription is the process of copying a segment of DNA into RNA for the purpose of gene expression. Some segments of DNA are transcribed into RNA molecules that can encode proteins, called messenger RNA (mRNA). Other segments of DNA are transc ...
in some
eukaryotic The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...
gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
promoters.


TBP gene family

TBP is a member of a small gene family of TBP-related factors. The first TBP-related factor (TRF/TRF1) was identified in the fruit fly
Drosophila ''Drosophila'' (), from Ancient Greek δρόσος (''drósos''), meaning "dew", and φίλος (''phílos''), meaning "loving", is a genus of fly, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or p ...
, but appears to be fly or insect-specific. Subsequently TBPL1/TRF2 was found in the genomes of many metazoans, whereas
vertebrate Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain. The vertebrates make up the subphylum Vertebra ...
genomes encode a third vertebrate family member, TBPL2/TRF3. In specific cell types or on specific promoters TBP can be replaced by one of these TBP-related factors, some of which interact with the TATA box similarly to TBP.


Role as transcription factor

TBP is a subunit of the eukaryotic general transcription factor TFIID. TFIID is the first protein to bind to DNA during the formation of the
transcription preinitiation complex The preinitiation complex (abbreviated PIC) is a complex of approximately 100 proteins that is necessary for the transcription (genetics), transcription of protein-coding genes in eukaryotes and archaea. The preinitiation complex positions RNA po ...
of
RNA polymerase II RNA polymerase II (RNAP II and Pol II) is a Protein complex, multiprotein complex that Transcription (biology), transcribes DNA into precursors of messenger RNA (mRNA) and most small nuclear RNA (snRNA) and microRNA. It is one of the three RNA pol ...
(RNA Pol II). As one of the few proteins in the preinitiation complex that binds DNA in a sequence-specific manner, it helps position RNA polymerase II over the
transcription start site Transcription is the process of copying a segment of DNA into RNA for the purpose of gene expression. Some segments of DNA are transcribed into RNA molecules that can encode proteins, called messenger RNA (mRNA). Other segments of DNA are transc ...
of the gene. However, it is estimated that only 10–20% of human promoters have TATA boxes - the majority of human promoters are TATA-less housekeeping gene promoters - so TBP is probably not the only protein involved in positioning RNA polymerase II.. The binding of TBP to these promoters is facilitated by housekeeping gene regulators. Interestingly, transcription initiates within a narrow region at around 30 bp downstream of TATA box on TATA-containing promoters, while transcription start sites of TATA-less promoters are dispersed within a 200 bp region. Binding of TFIID to the TATA box in the promoter region of the gene initiates the recruitment of other factors required for RNA Pol II to begin transcription. Some of the other recruited transcription factors include TFIIA, TFIIB, and TFIIF. Each of these transcription factors contains several protein subunits. TBP is also important for transcription by RNA polymerase I and RNA polymerase III, and is therefore involved in transcription initiation by all three RNA polymerases. TBP is involved in DNA melting (double strand separation) by bending the
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 ...
by 80° (the AT-rich sequence to which it binds facilitates easy melting). The TBP is an unusual protein in that it binds the minor groove using a β sheet. Another distinctive feature of TBP is a long string of glutamines in the N-terminus of the protein. This region modulates the DNA binding activity of the C-terminus, and modulation of DNA-binding affects the rate of transcription complex formation and initiation of transcription. Mutations that expand the number of CAG repeats encoding this polyglutamine tract, and thus increase the length of the polyglutamine string, are associated with spinocerebellar ataxia 17, a
neurodegenerative disorder A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their death. Neurodegenerative diseases include amyotrophic lateral sclerosis, mul ...
classified as a polyglutamine disease.


DNA-protein interactions

When TBP binds to a TATA box within the
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 ...
, it distorts the DNA by inserting amino acid side-chains between base pairs, partially unwinding the helix, and doubly kinking it. The distortion is accomplished through a great amount of surface contact between the protein and DNA. TBP binds with the negatively charged phosphates in the DNA backbone through positively charged
lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. Lysine contains an α-amino group (which is in the protonated form when the lysine is dissolved in water at physiological pH), an α-carboxylic acid group ( ...
and
arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidinium, guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) a ...
amino acid residues. The sharp bend in the DNA is produced through projection of four bulky
phenylalanine Phenylalanine (symbol Phe or F) is an essential α-amino acid with the chemical formula, formula . It can be viewed as a benzyl group substituent, substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of ...
residues into the minor groove. As the DNA bends, its contact with TBP increases, thus enhancing the DNA-protein interaction. The strain imposed on the DNA through this interaction initiates melting, or separation, of the strands. Because this region of DNA is rich in
adenine Adenine (, ) (nucleoside#List of nucleosides and corresponding nucleobases, symbol A or Ade) is a purine nucleotide base that is found in DNA, RNA, and Adenosine triphosphate, ATP. Usually a white crystalline subtance. The shape of adenine is ...
and
thymine Thymine () (symbol T or Thy) is one of the four nucleotide bases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine, guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidine ...
residues, which base-pair through only two
hydrogen bonds In chemistry, a hydrogen bond (H-bond) is a specific type of molecular interaction that exhibits partial covalent character and cannot be described as a purely electrostatic force. It occurs when a hydrogen (H) atom, covalently bonded to a mo ...
, the DNA strands are more easily separated. Separation of the two strands exposes the bases and allows
RNA polymerase II RNA polymerase II (RNAP II and Pol II) is a Protein complex, multiprotein complex that Transcription (biology), transcribes DNA into precursors of messenger RNA (mRNA) and most small nuclear RNA (snRNA) and microRNA. It is one of the three RNA pol ...
to begin transcription of the
gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
. TBP's C-terminus composes of a helicoidal shape that (incompletely) complements the T-A-T-A region of DNA. This incompleteness allows DNA to be passively bent on binding. For information on the use of TBP in cells see: RNA polymerase I,
RNA polymerase II RNA polymerase II (RNAP II and Pol II) is a Protein complex, multiprotein complex that Transcription (biology), transcribes DNA into precursors of messenger RNA (mRNA) and most small nuclear RNA (snRNA) and microRNA. It is one of the three RNA pol ...
, and RNA polymerase III.


Protein–protein interactions

TATA-binding protein has been shown to interact with: * BRF1, * BTAF1, * C-Fos, * C-jun, * EDF1, * GTF2B (TFIIB), * GTF2A1 ( TFIIA subunit 1), * GTF2F1 ( TFIIF subunit 1) * GTF2H4 ( TFIIH subunit 4), * Mdm2, * MSX1, * NFYB, * P53, * PAX6, * POLR2A, * POU2F1, * RELA, * NR2B1, * TAF1, * TAF4, * TAF5, * TAF6, * TAF7, * TAF9. * TAF10, * TAF11, * TAF13, and * TAF15.


Complex assembly

The TATA-box binding
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 ...
(TBP) is required for the initiation of transcription by RNA polymerases I, II and III, from promoters with or without a TATA box. In the presence of a TATA-less promoter, TBP binds with the help of TBP-associated factors (TAFs). TBP associates with a host of factors, including the general
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 TFIIA, -B, -D, -E, and -H, to form huge multi-subunit pre-initiation complexes on the core promoter. Through its association with different transcription factors, TBP can initiate transcription from different RNA
polymerase In biochemistry, a polymerase is an enzyme (Enzyme Commission number, EC 2.7.7.6/7/19/48/49) that synthesizes long chains of polymers or nucleic acids. DNA polymerase and RNA polymerase are used to assemble DNA and RNA molecules, respectively, by ...
s. There are several related TBPs, including TBP-like (TBPL)
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.


Structure

The C-terminal core of TBP (~180 residues) is highly conserved and contains two 88-amino acid repeats that produce a saddle-shaped
structure A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such as ...
that straddles the DNA; this region
bind BIND () is a suite of software for interacting with the Domain Name System (DNS). Its most prominent component, named (pronounced ''name-dee'': , short for ''name Daemon (computing), daemon''), performs both of the main DNS server roles, acting ...
s to the TATA box and interacts with
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 and regulatory
proteins Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, re ...
. By contrast, the N-terminal region varies in both length and
sequence In mathematics, a sequence is an enumerated collection of objects in which repetitions are allowed and order matters. Like a set, it contains members (also called ''elements'', or ''terms''). The number of elements (possibly infinite) is cal ...
.


References


External links


GeneReviews/NCBI/NIH/UW entry on Spinocerebellar Ataxia Type 17
* * * * {{DEFAULTSORT:Tata-Binding Protein Proteins Genes Transcription factors