| Structural highlights
Function
[TFAM_HUMAN] Binds to the mitochondrial light strand promoter and functions in mitochondrial transcription regulation. Required for accurate and efficient promoter recognition by the mitochondrial RNA polymerase. Promotes transcription initiation from the HSP1 and the light strand promoter by binding immediately upstream of transcriptional start sites. Is able to unwind DNA. Bends the mitochondrial light strand promoter DNA into a U-turn shape via its HMG boxes. Required for maintenance of normal levels of mitochondrial DNA. May play a role in organizing and compacting mitochondrial DNA.[1] [2] [3] [4] [5]
Publication Abstract from PubMed
Human mitochondrial transcription factor A, TFAM, is essential for mitochondrial DNA packaging and maintenance and also has a crucial role in transcription. Crystallographic analysis of TFAM in complex with an oligonucleotide containing the mitochondrial light strand promoter (LSP) revealed two high-mobility group (HMG) protein domains that, through different DNA recognition properties, intercalate residues at two inverted DNA motifs. This induced an overall DNA bend of ~180 degrees , stabilized by the interdomain linker. This U-turn allows the TFAM C-terminal tail, which recruits the transcription machinery, to approach the initiation site, despite contacting a distant DNA sequence. We also ascertained that structured protein regions contacting DNA in the crystal were highly flexible in solution in the absence of DNA. Our data suggest that TFAM bends LSP to create an optimal DNA arrangement for transcriptional initiation while facilitating DNA compaction elsewhere in the genome.
Human mitochondrial transcription factor A induces a U-turn structure in the light strand promoter.,Rubio-Cosials A, Sidow JF, Jimenez-Menendez N, Fernandez-Millan P, Montoya J, Jacobs HT, Coll M, Bernado P, Sola M Nat Struct Mol Biol. 2011 Oct 30;18(11):1281-9. doi: 10.1038/nsmb.2160. PMID:22037172[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Fisher RP, Lisowsky T, Parisi MA, Clayton DA. DNA wrapping and bending by a mitochondrial high mobility group-like transcriptional activator protein. J Biol Chem. 1992 Feb 15;267(5):3358-67. PMID:1737790
- ↑ Litonin D, Sologub M, Shi Y, Savkina M, Anikin M, Falkenberg M, Gustafsson CM, Temiakov D. Human mitochondrial transcription revisited: only TFAM and TFB2M are required for transcription of the mitochondrial genes in vitro. J Biol Chem. 2010 Jun 11;285(24):18129-33. doi: 10.1074/jbc.C110.128918. Epub, 2010 Apr 21. PMID:20410300 doi:http://dx.doi.org/10.1074/jbc.C110.128918
- ↑ Gangelhoff TA, Mungalachetty PS, Nix JC, Churchill ME. Structural analysis and DNA binding of the HMG domains of the human mitochondrial transcription factor A. Nucleic Acids Res. 2009 Jun;37(10):3153-64. Epub 2009 Mar 20. PMID:19304746 doi:10.1093/nar/gkp157
- ↑ Rubio-Cosials A, Sidow JF, Jimenez-Menendez N, Fernandez-Millan P, Montoya J, Jacobs HT, Coll M, Bernado P, Sola M. Human mitochondrial transcription factor A induces a U-turn structure in the light strand promoter. Nat Struct Mol Biol. 2011 Oct 30;18(11):1281-9. doi: 10.1038/nsmb.2160. PMID:22037172 doi:10.1038/nsmb.2160
- ↑ Ngo HB, Kaiser JT, Chan DC. The mitochondrial transcription and packaging factor Tfam imposes a U-turn on mitochondrial DNA. Nat Struct Mol Biol. 2011 Oct 30;18(11):1290-6. doi: 10.1038/nsmb.2159. PMID:22037171 doi:10.1038/nsmb.2159
- ↑ Rubio-Cosials A, Sidow JF, Jimenez-Menendez N, Fernandez-Millan P, Montoya J, Jacobs HT, Coll M, Bernado P, Sola M. Human mitochondrial transcription factor A induces a U-turn structure in the light strand promoter. Nat Struct Mol Biol. 2011 Oct 30;18(11):1281-9. doi: 10.1038/nsmb.2160. PMID:22037172 doi:10.1038/nsmb.2160
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