TATA binding protein

The TATA binding protein (TBP) is a transcription factor that binds specifically to a DNA sequence called the TATA box. This DNA sequence is found about 25-30 base pairs upstream of the transcription start site in some eukaryotic gene promoters.cite journal | author = Kornberg RD | title = The molecular basis of eukaryotic transcription | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 104 | issue = 32 | pages = 12955–61 | year = 2007 | pmid = 17670940 | doi = 10.1073/pnas.0704138104] TBP, along with a variety of TBP-associated factors, make up the TFIID, a general transcription factor that in turn makes up part of the RNA polymerase II preinitiation complex.cite journal | author = Lee TI, Young RA | title = Transcription of eukaryotic protein-coding genes | journal = Annu. Rev. Genet. | volume = 34 | issue = | pages = 77–137 | year = 2000 | pmid = 11092823 | doi = 10.1146/annurev.genet.34.1.77] As one of the few proteins in the preinitation complex that binds DNA in a sequence-specific manner, it helps position RNA polymerase II over the 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 DNA melting (double strand separation) by bending the 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 polyglutamine tract, and thus increase the length of the polyglutamine string, are associated with spinocerebellar ataxia 17, a neurodegenerative disorder classified as a polyglutamine disease. [cite web | title = Entrez Gene: TBP TATA box binding protein| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6908| accessdate = ]

Role as Transcription Factor Subunit

TBP is a subunit of the eukaryotic transcription factor TFIID. TFIID is the first protein to bind to DNA during the formation of the pre-initiation transcription complex of RNA polymerase II (RNA Pol II). 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 are formed from the interaction of many protein subunits, indicating that transcription is a heavily regulated process.

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

DNA-Protein Interactions

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

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

References

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External links

* [http://www.massey.ac.nz/~wwbioch/DNAprot/DNAmelt/framset.htm Interactive TBP Structure at massey.ac.nz]
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