TATA-binding protein

The TATA-binding protein (TBP) is a is_associated_with::general transcription factor that binds specifically to a is_associated_with::DNA sequence called the is_associated_with::TATA box. This DNA sequence is found about 30 is_associated_with::base pairs upstream of the is_associated_with::transcription start site in some eukaryotic is_associated_with::gene promoters. TBP, along with a variety of is_associated_with::TBP-associated factors, make up the is_associated_with::TFIID, a is_associated_with::general transcription factor that in turn makes up part of the is_associated_with::RNA polymerase II preinitiation complex. 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 is_associated_with::transcription start site of the gene. However, it is estimated that only 10-20% of human promoters have TATA boxes. Therefore, TBP is probably not the only protein involved in positioning RNA polymerase II.

TBP is involved in is_associated_with::DNA melting (double strand separation) by bending the is_associated_with::DNA 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 is_associated_with::polyglutamine tract, and thus increase the length of the polyglutamine string, are associated with is_associated_with::spinocerebellar ataxia 17, a is_associated_with::neurodegenerative disorder classified as a is_associated_with::polyglutamine disease.

Role as transcription factor
TBP is a subunit of the eukaryotic is_associated_with::transcription factor is_associated_with::TFIID. TFIID is the first protein to bind to DNA during the formation of the pre-initiation transcription complex of is_associated_with::RNA polymerase II (RNA Pol II). Binding of TFIID to the is_associated_with::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 is_associated_with::transcription factors include is_associated_with::TFIIA, is_associated_with::TFIIB, and is_associated_with::TFIIF. Each of these transcription factors is formed from the interaction of many protein subunits, indicating that transcription is a heavily regulated process.

TBP is also a necessary component of is_associated_with::RNA polymerase I and is_associated_with::RNA polymerase III, and is, it is thought, the only common subunit required by all three of the RNA polymerases.

DNA-Protein Interactions
When TBP binds to a is_associated_with::TATA box within the is_associated_with::DNA, 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 is_associated_with::lysine and is_associated_with::arginine amino acid residues. The sharp bend in the DNA is produced through projection of four bulky is_associated_with::phenylalanine 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 is_associated_with::adenine and is_associated_with::thymine residues, which base-pair through only two is_associated_with::hydrogen bonds, the DNA strands are more easily separated. Separation of the two strands exposes the bases and allows is_associated_with::RNA polymerase II to begin transcription of the is_associated_with::gene.

TBP's C-terminus composes of a helicoidal shape that (incompletely) complements the T-A-T-A region of DNA. It is interesting to note that this incompleteness allows DNA to be passively bent on binding.

For information on the use of TBP in cells see: is_associated_with::RNA polymerase I, is_associated_with::RNA polymerase II, and is_associated_with::RNA polymerase III.

Protein-Protein interactions
TATA-binding protein has been shown to interact with:


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

Complex Assembly
The TATA-box binding is_associated_with::protein (TBP) is required for the initiation of transcription by RNA is_associated_with::polymerases I, II and III, from promoters with or without a TATA box. TBP associates with a host of factors, including the general is_associated_with::transcription factors 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 is_associated_with::polymerases. There are several related TBPs, including TBP-like (TBPL) is_associated_with::proteins.

Structure
The C-terminal core of TBP (~180 residues) is highly conserved and contains two 77-amino acid repeats that produce a saddle-shaped structure that straddles the DNA; this region binds to the TATA box and interacts with is_associated_with::transcription factors and regulatory is_associated_with::proteins. By contrast, the N-terminal region varies in both length and sequence.