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Title | Organization of the human mitochondrial transcription initiation complex. |
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Journal, issue, pages | Nucleic Acids Res, Vol. 42, Issue 6, Page 4100-4112, Year 2014 |
Publish date | Jan 9, 2014 |
Authors | Elena Yakubovskaya / Kip E Guja / Edward T Eng / Woo Suk Choi / Edison Mejia / Dmitri Beglov / Mark Lukin / Dima Kozakov / Miguel Garcia-Diaz / |
PubMed Abstract | Initiation of transcription in human mitochondria involves two factors, TFAM and TFB2M, in addition to the mitochondrial RNA polymerase, POLRMT. We have investigated the organization of the human ...Initiation of transcription in human mitochondria involves two factors, TFAM and TFB2M, in addition to the mitochondrial RNA polymerase, POLRMT. We have investigated the organization of the human mitochondrial transcription initiation complex on the light-strand promoter (LSP) through solution X-ray scattering, electron microscopy (EM) and biochemical studies. Our EM results demonstrate a compact organization of the initiation complex, suggesting that protein-protein interactions might help mediate initiation. We demonstrate that, in the absence of DNA, only POLRMT and TFAM form a stable interaction, albeit one with low affinity. This is consistent with the expected transient nature of the interactions necessary for initiation and implies that the promoter DNA acts as a scaffold that enables formation of the full initiation complex. Docking of known crystal structures into our EM maps results in a model for transcriptional initiation that strongly correlates with new and existing biochemical observations. Our results reveal the organization of TFAM, POLRMT and TFB2M around the LSP and represent the first structural characterization of the entire mitochondrial transcriptional initiation complex. |
External links | Nucleic Acids Res / PubMed:24413562 / PubMed Central |
Methods | EM (single particle) |
Resolution | 25.0 Å |
Structure data | EMDB-2529: |
Source |
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