Structural biology of TBP

TBP sequences are available from the NCBI server (www.ncbi.nlm.nih.gov/) for organisms representing archaea and the four kingdoms of eukarya. In all cases, the amino acid sequences contain a conserved C-terminal domain of 180 amino acids, and a variable N-terminus, ranging from 1 to 172 residues. The C-terminal domain appears to have arisen by duplication of an ancestor protein before the separation of archaea and eukarya, dividing this domain in two subdomains with -40% identity in sequence [1]. 

Crystal structures have been obtained for Ae C-terminal domain of free TBP from three different species (P.woesei [IS], Ajhaliana [19,20], and S.cerevisiae [21]), revealing a saddle-like structure with stirrups formed by a 10-stranded P-sheet and four a-helices, reflecting the imperfect repeats found in the sequence. All these structures crystallized as dimers, and the dimerization 

Ternary complexes formed by TBP, DNA and TFIIA or TFIIB have also been crystallized [27-32] and their structures are available in the PDB and NDB (see Table 1). These complexes display practically the same mode of interaction between TBP and the DNA moiety as found in the corresponding binary complexes. They also explain the inability of TFIIB to bind to DNA on its own, as it is found to contact the DNA upstream and downstream of TBP, an impossible feat in a straight DNA molecule. This feature places TBP among the architectural transcription factors, together with DBF, HMG, SRY and LEFl 

The largest TAP included in TFIID has an inhibitory action on TBP binding to DNA. The structure of a domain located in the N-terminus of D. melanogaster TAF230 complexed with S.cerevisiae TBP was obtained by NMR 

MLP d(CTATAAAAGGGC) CYCl d(GTATATAAAACG) E4 d(CGTATATATACG) EFla d(ACTTTTTAAAGC) T6 + BRE d(AGAGTAAAGTrTAAATACTTATAT). 

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