Sandbox TATA Binding Protein Austin McCauley

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Function

TATA binding protein(TBP) is one of several proteins which make up the RNA polymerase complex used in transcription. Specifically the TBP belongs to the TFIID complex containing a variety of transcription factors contributing to success of transcription for the RNA polymerase complex. TBP is involved in all three RNA polymerase complexes, making TBP an essential initiation factor in transcription. (BIOCHEMISTRY AND STRUCTURAL BIOLOGY OF TRANSCRIPTION FACTOR IID (TFIID)) The TFIID focuses on binding to the DNA used in transcription. The TBP's main function is to bind with the TATA box of the DNA in order to anchor the protein to the TFIID complex, thus allowing for RNA II polymerase to carry out transcription. (TATA element recognition by the TATA box-binding protein has been conserved throughout evolution) The importance of the TBP in the RNA polymerase complex stems from the RNA polymerase complex's inability to recognize the target promoter directly. The TBP binds to the TATA sequence approximately 25 base pairs upstream the start site of the DNA.(BIOCHEMISTRY AND STRUCTURAL BIOLOGY OF TRANSCRIPTION FACTOR IID (TFIID))

Interaction with DNA with Key Structures

The TBP is dimer, with both monomers having the ability to interact with the DNA's TATA sequence. The TBP has a conserved core segment, C-terminal portion, of residues found in a wide range of organisms.(Biochemistry and structural biology of transcription factor IID (TFIID).) The monomer contains tertiary protein structures of both alpha helices and beta sheets. The combination of both alpha helices and beta sheets result in saddle shape. The shape of the protein plays a significant role in how it binds and interacts with DNA. The concave shape of the binding site forms from the antiparallel beta sheet, meanwhile the the alpha helices on the non DNA binding surface interact with other transcription factors.(http://www.ncbi.nlm.nih.gov/pmc/articles/PMC317201/)(2.1 A resolution refined structure of a TATA box-binding protein (TBP)). The binding surface of the concave portion of the TBP has mostly hydrophobic residues. The hydrophobic residues interact with the minor groove of the DNA and place phenylalanine side chains between base pairs causing kinks.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC317201/). The recognized mechanism for binding between TBP and DNA is an induced fit mechanism. The induced fit mechanism comes from the concave surface previously mentioned, here the minor groove and phosphate-ribose all make contact. The DNA continues to enter the binding site of the TBP as the phenylalanines partially unwind the double helix starting at the first T:A base pair of the DNA. (http://www.annualreviews.org/doi/pdf/10.1146/annurev.bi.65.070196.004005.) The partially unwound DNA allows for the protein to slightly bend the DNA and provides a greater interface between the DNA and protein. The greater surface area makes interactions between the TBP and DNA more favorable. TBP also deomnstrates a conformational change upon binding to the DNA. When binding occurs between the DNA and TBP, the TBP twists one of its domains. The RNA polymerase complex recognizes the TBP/TFIID complex and contiues transcription. (http://www.annualreviews.org/doi/pdf/10.1146/annurev.bi.65.070196.004005)

The phenylalanine residues play a key role in TBP binding to the DNA, but other residues contribute to the interaction between TBP and DNA. The following residues interact with the DNA providing stability and allowing the TBP to anchor the DNA for further proteins to perform transcription. These other interactive residues are Arg154 which contacts the sense strand backbone, and Glu 51, Lys85 and 169, and phosphates play a role in stabalizing the DNA TBP interaction.(http://onlinelibrary.wiley.com/doi/10.1002/bip.10409/full#fig5)

Structural highlights