Structure of the human mitochondrial transcription initiation complex at the HSP promoterStructure of the human mitochondrial transcription initiation complex at the HSP promoter

Structural highlights

6erq is a 10 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Activity:DNA-directed RNA polymerase, with EC number 2.7.7.6
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[RPOM_HUMAN] DNA-dependent RNA polymerase catalyzes the transcription of mitochondrial DNA into RNA using the four ribonucleoside triphosphates as substrates.[1] [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.[2] [3] [4] [5] [6] [TFB2M_HUMAN] S-adenosyl-L-methionine-dependent methyltransferase which specifically dimethylates mitochondrial 12S rRNA at the conserved stem loop. Also required for basal transcription of mitochondrial DNA, probably via its interaction with POLRMT and TFAM. Stimulates transcription independently of the methyltransferase activity. Compared to TFB1M, it activates transcription of mitochondrial DNA more efficiently, while it has less methyltransferase activity.[7] [8] [9] [10]

References

  1. Minczuk M, He J, Duch AM, Ettema TJ, Chlebowski A, Dzionek K, Nijtmans LG, Huynen MA, Holt IJ. TEFM (c17orf42) is necessary for transcription of human mtDNA. Nucleic Acids Res. 2011 May;39(10):4284-99. doi: 10.1093/nar/gkq1224. Epub 2011, Jan 28. PMID:21278163 doi:10.1093/nar/gkq1224
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. Falkenberg M, Gaspari M, Rantanen A, Trifunovic A, Larsson NG, Gustafsson CM. Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA. Nat Genet. 2002 Jul;31(3):289-94. Epub 2002 Jun 17. PMID:12068295 doi:http://dx.doi.org/10.1038/ng909
  8. McCulloch V, Shadel GS. Human mitochondrial transcription factor B1 interacts with the C-terminal activation region of h-mtTFA and stimulates transcription independently of its RNA methyltransferase activity. Mol Cell Biol. 2003 Aug;23(16):5816-24. PMID:12897151
  9. Gaspari M, Falkenberg M, Larsson NG, Gustafsson CM. The mitochondrial RNA polymerase contributes critically to promoter specificity in mammalian cells. EMBO J. 2004 Nov 24;23(23):4606-14. Epub 2004 Nov 4. PMID:15526033 doi:http://dx.doi.org/7600465
  10. 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

6erq, resolution 4.50Å

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