Yeast TATA Binding Protein

Overview

The 2.5 Å crystal structure of a TATA-box complex with yeast TATA-box-binding protein (TBP) is shown at the right ( is a two chain structure with sequence from Saccharomyces cerevisiae that is bound to the TATA-box complex of DNA). ^[1] A key initial step in TATA-box promoters is the recognition by TBP of the ^[2] TBP initiates strand separation on binding to DNA. ^[2] As a key factor in the transcription preinitiation complex, TBP helps situate the RNA polymerase II over a gene’s transcription start site. ^[2]

Structure

Its characteristic consists of two similar domains. The saddle-shape of TBP provides docking sites that allow other transcription factors and proteins to bind. ^[2] TBP and numerous TBP-associated factors interact to make TFIID, a transcription factor that is part of the active RNA polymerase II transcription complex. ^[2] TBP is a 30-kd component of the 700-kd TFIID complex. ^[2] TBP-DNA interactions contain many important structural features. One important feature of the TBP is that its long dimension follows the trajectory of the minor groove of the DNA. ^[3] TBP interacts with the DNA through the concave side of the ^[1] Conserved between the two subdomains are that lie along the edges of the protein in proximity to the phosphates in DNA. ^[3] Down the middle of the groove between the two rows of basic residues lies a band of hydrophobic residues runs down the center of the DNA-binding surface. ^[3]

Mechanism for Binding to DNA

The concave surface of TBP is the site where eight base pairs of the TATA box of DNA binds. ^[1] On binding, it induces large conformation changes in the bound DNA where it bends the major groove of DNA with unprecedented severity and causes the double helix to become significantly underwound. ^[1] The purpose of the conformation changes is to widen the double helix’s minor groove, which allows the DNA to render extensive contact with the antiparallel β strands that are located on the concave side of the TBP. ^[2] The main types of interactions at this interface are hydrophobic interactions between the minor groove and the entire ^[2] At the binding site, intercalate themselves between the TATA box base pairs on the DNA. ^[2] The resulting severe bend and positive writhe alters the trajectory of the flanking B-form DNA. ^[1] The are involved in the function of recruiting TFIIA. ^[4]

Role as Transcription Factor Subunit

TBP acts as a 30-kd subunit of the 700-kd eukaryotic transcription factor TFIID. ^[2] TBP and a variety of TBP-associated factors, make up the TFIID, which in turn makes up part of the RNA polymerase II preinitiation complex. ^[2] During the formation of the preinitiation transcription complex of RNA polymerase II, TFIID is the first protein to bind to DNA. ^[2] The recruitment of other factors required for RNA Polymerase II to initiate transcription results from the binding of TFIID to the TATA box in the promoter region of the gene. ^[2] The surface of the TBP saddle provides docking sites for the binding of other transcription factors. ^[2] TFIIA is recruited and interacts primarily with the TBP. ^[2] TFIIB and TFIIF are recruited and are followed by the RNA polymerase II, TFIIE, and TFIIH. This results in the formation of the basal transcription apparatus. ^[2]