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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 beta-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.

SUBMITTER: Doi-Katayama Y

PROVIDER: S-EPMC2203370 | biostudies-literature | 2007 Aug

REPOSITORIES: biostudies-literature

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

Doi-Katayama Yukiko Y Hayashi Fumiaki F Inoue Makoto M Yabuki Takashi T Aoki Masaaki M Seki Eiko E Matsuda Takayoshi T Kigawa Takanori T Yoshida Mayumi M Shirouzu Mikako M Terada Takaho T Hayashizaki Yoshihide Y Yokoyama Shigeyuki S Hirota Hiroshi H

Protein science : a publication of the Protein Society 20070628 8

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 ...[more]

PMID: 17600150

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Project description:UnlabelledModulation of host cell transcription, translation, and posttranslational modification processes is critical for the ability of many viruses to replicate efficiently within host cells. The human adenovirus (Ad) early region 4 open reading frame 3 (E4-ORF3) protein forms unique inclusions throughout the nuclei of infected cells and inhibits the antiviral Mre11-Rad50-Nbs1 DNA repair complex through relocalization. E4-ORF3 also induces SUMOylation of Mre11 and Nbs1. We recently identified additional cellular targets of E4-ORF3 and found that E4-ORF3 stimulates ubiquitin-like modification of 41 cellular proteins involved in a wide variety of processes. Among the proteins most abundantly modified in an E4-ORF3-dependent manner was the general transcription factor II-I (TFII-I). Analysis of Ad-infected cells revealed that E4-ORF3 induces TFII-I relocalization and SUMOylation early during infection. In the present study, we explored the relationship between E4-ORF3 and TFII-I. We found that Ad infection or ectopic E4-ORF3 expression leads to SUMOylation of TFII-I that precedes a rapid decline in TFII-I protein levels. We also show that E4-ORF3 is required for ubiquitination of TFII-I and subsequent proteasomal degradation. This is the first evidence that E4-ORF3 regulates ubiquitination. Interestingly, we found that E4-ORF3 modulation of TFII-I occurs in diverse cell types but only E4-ORF3 of Ad species C regulates TFII-I, providing critical insight into the mechanism by which E4-ORF3 targets TFII-I. Finally, we show that E4-ORF3 stimulates the activity of a TFII-I-repressed viral promoter during infection. Our results characterize a novel mechanism of TFII-I regulation by Ad and highlight how a viral protein can modulate a critical cellular transcription factor during infection.ImportanceAdenovirus has evolved a number of mechanisms to target host signaling pathways in order to optimize the cellular environment during infection. E4-ORF3 is a small viral protein made early during infection, and it is critical for inactivating host antiviral responses. In addition to its ability to capture and reorganize cellular proteins, E4-ORF3 also regulates posttranslational modifications of target proteins, but little is known about the functional consequences of these modifications. We recently identified TFII-I as a novel target of E4-ORF3 that is relocalized into dynamic E4-ORF3 nuclear structures and subjected to E4-ORF3-mediated SUMO modification. Here, we show that TFII-I is targeted by E4-ORF3 for ubiquitination and proteasomal degradation and that E4-ORF3 stimulates gene expression from a TFII-I-repressed viral promoter. Our findings suggest that the specific targeting of TFII-I by E4-ORF3 is a mechanism to inactivate its antiviral properties. These studies provide further insight into how E4-ORF3 functions to counteract host antiviral responses.

Dataset Information

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

Publications

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

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