Download Initiatior (Inr) motif

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Initiatior (Inr) motif
The Initiatior (Inr) motif is a DNA transcription promoter that is similar in function to the
Pribnow box (for prokaryotes) or the TATA box (for eukaryotes). It has the consensus sequence
YYAN(T/A)YY,where Y stands for any pyrimidine (cytosine or thymine). Similarly to the
TATA box, the Inr motif facilitates the binding of Transcription Factor II D (TBP).
TATA binding protein (TBP)
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. TBP, along with a variety of TBPassociated factors, make up the TFIID, a general transcription factor that in turn makes up
part of the RNA polymerase II pre-initiation complex. 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 1020% 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 ATrich 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.
β sheet
The β sheet (also β-pleated sheet) is the second form of regular secondary structure in proteins
consisting of beta strands connected laterally by three or more hydrogen bonds, forming a generally
twisted, pleated sheet (the most common form of regular secondary structure in proteins is the alpha
helix). A beta strand (also β-strand) is a stretch of amino acids typically 5–10 amino acids long
whose peptide backbones are almost fully extended. The association of beta sheets has been
implicated in the formation of protein aggregates and fibrils observed in many human
diseases, notably the amyloidoses.