Structural analysis and DNA binding of the HMG domains of the human mitochondrial transcription factor A
- Univ. of Colorado, Denver, CO (United States). Dept. of Pharmacology; Univ. of Colorado, Denver, CO (United States). Molecular Biology Program; DOE/OSTI
- Univ. of Colorado, Denver, CO (United States). Dept. of Pharmacology
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Advanced Light Source (ALS). Molecular Biology Consortium. Beamline 4.2.2
- Univ. of Colorado, Denver, CO (United States). Dept. of Pharmacology; Univ. of Colorado, Denver, CO (United States). Molecular Biology Program
The mitochondrial transcription factor A (mtTFA) is central to assembly and initiation of the mitochondrial transcription complex. Human mtTFA (h-mtTFA) is a dual high mobility group box (HMGB) protein that binds site-specifically to the mitochondrial genome and demarcates the promoters for recruitment of h-mtTFB1, h-mtTFB2 and the mitochondrial RNA polymerase. The stoichiometry of h-mtTFA was found to be a monomer in the absence of DNA, whereas it formed a dimer in the complex with the light strand promoter (LSP) DNA. Each of the HMG boxes and the C-terminal tail were evaluated for their ability to bind to the LSP DNA. Removal of the C-terminal tail only slightly decreased nonsequence specific DNA binding, and box A, but not box B, was capable of binding to the LSP DNA. The X-ray crystal structure of h-mtTFA box B, at 1.35 Å resolution, revealed the features of a noncanonical HMG box. Interactions of box B with other regions of h-mtTFA were observed. Together, these results provide an explanation for the unusual DNA-binding properties of box B and suggest possible roles for this domain in transcription complex assembly.
- Research Organization:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
- Grant/Contract Number:
- AC02-05CH11231
- OSTI ID:
- 1625461
- Journal Information:
- Nucleic Acids Research, Journal Name: Nucleic Acids Research Journal Issue: 10 Vol. 37; ISSN 0305-1048
- Publisher:
- Oxford University PressCopyright Statement
- Country of Publication:
- United States
- Language:
- English
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