Solution structure of the general transcription factor 2I domain in mouse TFII‐I protein

Abstract

The general transcription factor TFII-I, with the corresponding gene name GTF2I, is an unusual transcriptional regulator that associates with both basal and signal-induced transcription factors. TFII-I consists of six GTF2I repeat domains, called I-repeats R1-R6. The structure and function of the GTF2I domain are not clearly understood, even though it contains a helix-loop-helix motif, which is considered to be the protein-protein interaction area, based on biochemical analyses. Here, we report the solution structure of the fifth repeat of the six GTF2I repeat domains from murine TFII-I, which was determined by heteronuclear multidimensional NMR spectroscopy (PDB code 1Q60). The three-dimensional structure of the GTF2I domain is classified as a new fold, consisting of four helices (residues 8-24, 34-39, 63-71, and 83-91), two antiparallel beta strands (residues 44-47 and 77-80), and a well-defined loop containing two b-turns between sheet 1 and helix 3. All of the repeats probably have similar folds to that of repeat 5, because the conserved residues in the GTF2I repeat domains are assembled on the hydrophobic core, turns, and secondary structure elements, as revealed by a comparison of the sequences of the first through the sixth GTF2I repeats in TFII-I.

A specific missense mutation in GTF2I occurs at high frequency in thymic epithelial tumors

“…It is possible that the p.Leu404His alteration will disrupt the hydrophobic interaction of Leu404 with either a hydrophobic site in the interacting partner protein(s) or within TFII-I, which has not yet been crystallized. However, the three-dimensional (3D) structure of the fifth I repeat of mouse TFII-I has been solved by nuclear magnetic resonance spectroscopy 16 . More recently, the structure of the third human repeat of TFII-I has been deposited in 3D Macromolecular Structures (NCBI database) by the same group.…”

Biochemistry and biology of the inducible multifunctional transcription factor TFII-I: 10years later

“…However, there are differences between TFII-I HLH motifs and traditional HLH motifs noted both by structure prediction and actual determination of solution structure of one of the TFII-I repeats. For instance, NMR spectroscopic determination of the three-dimensional structure of the fifth repeat in TFII-I revealed that the TFII-I/GFT2I domain consists of four helices, two anti-parallel strands/sheets (between helices 2 and 3 and between helices 3 and 4) and a long loop comprising of two β-turns between helices 2 and 3 (Fig 1c) (Doi-Katyama et al, 2007). It is likely that all other repeats of TFII-I have similar folds (henceforth called the “I-fold”) because the conserved residues commonly present in the various repeats are assembled on the hydrophobic core, β-turns and other secondary structural elements (Doi-Katyama et al, 2007).…”

Alternative splicing and promoter use in TFII-I genes

“…Structural analysis revealed that unusual repeated combinations of two exons encode protein domains specific to the TFII-I family and referred as I-repeats. I-repeats have an atypical helix-loop-helix structure that has been resolved by protein crystal analysis (Doi-Katayama et al, 2007) and can serve as independent DNA-binding modules with various DNA-binding efficiency (Vullhorst and Buonanno, 2005). GTF2I and GTF2IRD1 genes contain 6 and 5 I-repeats, respectively (Fig.…”