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| ==Structure of the human mitochondrial transcription initiation complex at the LSP promoter== | | ==Structure of the human mitochondrial transcription initiation complex at the LSP promoter== |
| <StructureSection load='6erp' size='340' side='right' caption='[[6erp]], [[Resolution|resolution]] 4.50Å' scene=''> | | <StructureSection load='6erp' size='340' side='right'caption='[[6erp]], [[Resolution|resolution]] 4.50Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6erp]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ERP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ERP FirstGlance]. <br> | | <table><tr><td colspan='2'>[[6erp]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ERP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ERP FirstGlance]. <br> |
| </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TFAM, TCF6, TCF6L2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), POLRMT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TFB2M, NS5ATP5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 4.502Å</td></tr> |
| <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-directed_RNA_polymerase DNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.6 2.7.7.6] </span></td></tr>
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6erp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6erp OCA], [https://pdbe.org/6erp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6erp RCSB], [https://www.ebi.ac.uk/pdbsum/6erp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6erp ProSAT]</span></td></tr> |
| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6erp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6erp OCA], [http://pdbe.org/6erp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6erp RCSB], [http://www.ebi.ac.uk/pdbsum/6erp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6erp ProSAT]</span></td></tr> | |
| </table> | | </table> |
| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/RPOM_HUMAN RPOM_HUMAN]] DNA-dependent RNA polymerase catalyzes the transcription of mitochondrial DNA into RNA using the four ribonucleoside triphosphates as substrates.<ref>PMID:21278163</ref> [[http://www.uniprot.org/uniprot/TFAM_HUMAN 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.<ref>PMID:1737790</ref> <ref>PMID:20410300</ref> <ref>PMID:19304746</ref> <ref>PMID:22037172</ref> <ref>PMID:22037171</ref> [[http://www.uniprot.org/uniprot/TFB2M_HUMAN 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.<ref>PMID:12068295</ref> <ref>PMID:12897151</ref> <ref>PMID:15526033</ref> <ref>PMID:20410300</ref> | | [https://www.uniprot.org/uniprot/TFAM_HUMAN 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.<ref>PMID:1737790</ref> <ref>PMID:20410300</ref> <ref>PMID:19304746</ref> <ref>PMID:22037172</ref> <ref>PMID:22037171</ref> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Transcription in human mitochondria is driven by a single-subunit, factor-dependent RNA polymerase (mtRNAP). Despite its critical role in both expression and replication of the mitochondrial genome, transcription initiation by mtRNAP remains poorly understood. Here, we report crystal structures of human mitochondrial transcription initiation complexes assembled on both light and heavy strand promoters. The structures reveal how transcription factors TFAM and TFB2M assist mtRNAP to achieve promoter-dependent initiation. TFAM tethers the N-terminal region of mtRNAP to recruit the polymerase to the promoter whereas TFB2M induces structural changes in mtRNAP to enable promoter opening and trapping of the DNA non-template strand. Structural comparisons demonstrate that the initiation mechanism in mitochondria is distinct from that in the well-studied nuclear, bacterial, or bacteriophage transcription systems but that similarities are found on the topological and conceptual level. These results provide a framework for studying the regulation of gene expression and DNA replication in mitochondria.
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| Structural Basis of Mitochondrial Transcription Initiation.,Hillen HS, Morozov YI, Sarfallah A, Temiakov D, Cramer P Cell. 2017 Nov 16;171(5):1072-1081.e10. doi: 10.1016/j.cell.2017.10.036. PMID:29149603<ref>PMID:29149603</ref>
| | ==See Also== |
| | | *[[RNA polymerase 3D structures|RNA polymerase 3D structures]] |
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 6erp" style="background-color:#fffaf0;"></div>
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| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: DNA-directed RNA polymerase]] | | [[Category: Homo sapiens]] |
| [[Category: Human]] | | [[Category: Large Structures]] |
| [[Category: Cramer, P]] | | [[Category: Cramer P]] |
| [[Category: Hillen, H S]] | | [[Category: Hillen HS]] |
| [[Category: Morozov, Y I]] | | [[Category: Morozov YI]] |
| [[Category: Sarfallah, A]] | | [[Category: Sarfallah A]] |
| [[Category: Temiakov, D]] | | [[Category: Temiakov D]] |
| [[Category: Initiation]]
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| [[Category: Mitochondria]]
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| [[Category: Polymerase]]
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| [[Category: Transcription]]
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