6o9l: Difference between revisions

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== Structural highlights ==

<table><tr><td colspan='2'>[[6o9l]] 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=6O9L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6O9L FirstGlance]. <br>

<table><tr><td colspan='2'>[[6o9l]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O9L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6O9L FirstGlance]. <br>

</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 7.2Å</td></tr>

<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG~~</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4~~</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>

<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=6o9l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o9l OCA], [https://pdbe.org/6o9l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6o9l RCSB], [https://www.ebi.ac.uk/pdbsum/6o9l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6o9l ProSAT]</span></td></tr>

</table>

== Function ==

[https://www.uniprot.org/uniprot/~~RPB1_HUMAN RPB1_HUMAN~~] ~~DNA~~-dependent ~~RNA polymerase catalyzes~~ the ~~transcription of DNA into RNA using~~ the ~~four ribonucleoside triphosphates as substrates~~. ~~Largest~~ and ~~catalytic component~~ of ~~RNA polymerase II which synthesizes mRNA precursors~~ and ~~many functional non~~-~~coding RNAs~~. ~~Forms~~ the ~~polymerase active center together with~~ the ~~second largest subunit~~. ~~Pol II is~~ the ~~central component of~~ the basal RNA polymerase II ~~transcription machinery. It is composed~~ of ~~mobile elements that move relative to each other. RPB1 is part~~ of ~~the core element with the central~~ large ~~cleft~~, the ~~clamp element that moves to open~~ and ~~close~~ the ~~cleft~~ and ~~the jaws that~~ are ~~thought to grab~~ the ~~incoming~~ DNA ~~template. At~~ the ~~start~~ of transcription, ~~a single stranded~~ DNA ~~template strand of the promoter is positioned within~~ the ~~central active site cleft~~ of ~~Pol II~~. ~~A bridging helix emanates from RPB1 and crosses the cleft near the catalytic site and is thought~~ to ~~promote translocation of Pol II~~ by ~~acting as~~ a ~~ratchet~~ that ~~moves~~ the ~~RNA~~-~~DNA hybrid through the active site by switching from straight~~ to ~~bent conformations at each step of nucleotide addition~~. ~~During transcription elongation~~, ~~Pol II moves on~~ the ~~template as the transcript elongates~~. ~~Elongation is influenced by the phosphorylation status of~~ the ~~C-terminal domain (CTD) of~~ Pol II ~~largest subunit (RPB1)~~, ~~which serves as a platform for assembly of factors~~ that ~~regulate transcription initiation~~, ~~elongation~~, ~~termination and mRNA processing~~. ~~Acts as a RNA~~-~~dependent RNA polymerase when associated with small delta antigen of Hepatitis delta virus~~, ~~acting both as a replicate and transcriptase for the viral RNA circular genome~~.<ref>PMID:~~9852112~~</ref> <~~ref~~>~~PMID~~:~~18032511~~</~~ref~~>

[https://www.uniprot.org/uniprot/CDK7_HUMAN CDK7_HUMAN] Serine/threonine kinase involved in cell cycle control and in RNA polymerase II-mediated RNA transcription. Cyclin-dependent kinases (CDKs) are activated by the binding to a cyclin and mediate the progression through the cell cycle. Each different complex controls a specific transition between 2 subsequent phases in the cell cycle. Required for both activation and complex formation of CDK1/cyclin-B during G2-M transition, and for activation of CDK2/cyclins during G1-S transition (but not complex formation). CDK7 is the catalytic subunit of the CDK-activating kinase (CAK) complex. Phosphorylates SPT5/SUPT5H, SF1/NR5A1, POLR2A, p53/TP53, CDK1, CDK2, CDK4, CDK6 and CDK11B/CDK11. CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation, thus regulating cell cycle progression. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the repetitive C-terminus domain (CTD) of its large subunit (POLR2A), allowing its escape from the promoter and elongation of the transcripts. Phosphorylation of POLR2A in complex with DNA promotes transcription initiation by triggering dissociation from DNA. Its expression and activity are constant throughout the cell cycle. Upon DNA damage, triggers p53/TP53 activation by phosphorylation, but is inactivated in turn by p53/TP53; this feedback loop may lead to an arrest of the cell cycle and of the transcription, helping in cell recovery, or to apoptosis. Required for DNA-bound peptides-mediated transcription and cellular growth inhibition.<ref>PMID:9372954</ref> <ref>PMID:9840937</ref> <ref>PMID:10024882</ref> <ref>PMID:11113184</ref> <ref>PMID:16327805</ref> <ref>PMID:17386261</ref> <ref>PMID:17373709</ref> <ref>PMID:17901130</ref> <ref>PMID:19450536</ref> <ref>PMID:19015234</ref> <ref>PMID:19667075</ref> <ref>PMID:19136461</ref> <ref>PMID:19071173</ref> <ref>PMID:20360007</ref>

== Publication Abstract from PubMed ==

Transcription preinitiation complexes (PICs) are vital assemblies whose function underlies the expression of protein-encoding genes. Cryo-EM advances have begun to uncover their structural organization. Nevertheless, functional analyses are hindered by incompletely modeled regions. Here we integrate all available cryo-EM data to build a practically complete human PIC structural model. This enables simulations that reveal the assembly's global motions, define PIC partitioning into dynamic communities and delineate how structural modules function together to remodel DNA. We identify key TFIIE-p62 interactions that link core-PIC to TFIIH. p62 rigging interlaces p34, p44 and XPD while capping the DNA-binding and ATP-binding sites of XPD. PIC kinks and locks substrate DNA, creating negative supercoiling within the Pol II cleft to facilitate promoter opening. Mapping disease mutations associated with xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome onto defined communities reveals clustering into three mechanistic classes that affect TFIIH helicase functions, protein interactions and interface dynamics.

Transcription preinitiation complex structure and dynamics provide insight into genetic diseases.,Yan C, Dodd T, He Y, Tainer JA, Tsutakawa SE, Ivanov I Nat Struct Mol Biol. 2019 May 20. pii: 10.1038/s41594-019-0220-3. doi:, 10.1038/s41594-019-0220-3. PMID:31110295<ref>PMID:31110295</ref>

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

</div>

==See Also==

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Line 33:

[[Category: Homo sapiens]]

[[Category: Large Structures]]

[[Category: Synthetic construct]]

[[Category: Dodd T]]

[[Category: He Y]]

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@@ Line 3: / Line 3: @@
 <SX load='6o9l' size='340' side='right' viewer='molstar' caption='[[6o9l]], [[Resolution|resolution]] 7.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6o9l]] 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=6O9L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6O9L FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6o9l]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O9L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6O9L FirstGlance]. <br>
 </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 7.2&#8491;</td></tr>
-<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=6o9l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o9l OCA], [https://pdbe.org/6o9l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6o9l RCSB], [https://www.ebi.ac.uk/pdbsum/6o9l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6o9l ProSAT]</span></td></tr>
 </table>
 == Function ==
-[https://www.uniprot.org/uniprot/RPB1_HUMAN RPB1_HUMAN] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Largest and catalytic component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Forms the polymerase active center together with the second largest subunit. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB1 is part of the core element with the central large cleft, the clamp element that moves to open and close the cleft and the jaws that are thought to grab the incoming DNA template. At the start of transcription, a single stranded DNA template strand of the promoter is positioned within the central active site cleft of Pol II. A bridging helix emanates from RPB1 and crosses the cleft near the catalytic site and is thought to promote translocation of Pol II by acting as a ratchet that moves the RNA-DNA hybrid through the active site by switching from straight to bent conformations at each step of nucleotide addition. During transcription elongation, Pol II moves on the template as the transcript elongates. Elongation is influenced by the phosphorylation status of the C-terminal domain (CTD) of Pol II largest subunit (RPB1), which serves as a platform for assembly of factors that regulate transcription initiation, elongation, termination and mRNA processing. Acts as a RNA-dependent RNA polymerase when associated with small delta antigen of Hepatitis delta virus, acting both as a replicate and transcriptase for the viral RNA circular genome.<ref>PMID:9852112</ref> <ref>PMID:18032511</ref>
+[https://www.uniprot.org/uniprot/CDK7_HUMAN CDK7_HUMAN] Serine/threonine kinase involved in cell cycle control and in RNA polymerase II-mediated RNA transcription. Cyclin-dependent kinases (CDKs) are activated by the binding to a cyclin and mediate the progression through the cell cycle. Each different complex controls a specific transition between 2 subsequent phases in the cell cycle. Required for both activation and complex formation of CDK1/cyclin-B during G2-M transition, and for activation of CDK2/cyclins during G1-S transition (but not complex formation). CDK7 is the catalytic subunit of the CDK-activating kinase (CAK) complex. Phosphorylates SPT5/SUPT5H, SF1/NR5A1, POLR2A, p53/TP53, CDK1, CDK2, CDK4, CDK6 and CDK11B/CDK11. CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation, thus regulating cell cycle progression. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the repetitive C-terminus domain (CTD) of its large subunit (POLR2A), allowing its escape from the promoter and elongation of the transcripts. Phosphorylation of POLR2A in complex with DNA promotes transcription initiation by triggering dissociation from DNA. Its expression and activity are constant throughout the cell cycle. Upon DNA damage, triggers p53/TP53 activation by phosphorylation, but is inactivated in turn by p53/TP53; this feedback loop may lead to an arrest of the cell cycle and of the transcription, helping in cell recovery, or to apoptosis. Required for DNA-bound peptides-mediated transcription and cellular growth inhibition.<ref>PMID:9372954</ref> <ref>PMID:9840937</ref> <ref>PMID:10024882</ref> <ref>PMID:11113184</ref> <ref>PMID:16327805</ref> <ref>PMID:17386261</ref> <ref>PMID:17373709</ref> <ref>PMID:17901130</ref> <ref>PMID:19450536</ref> <ref>PMID:19015234</ref> <ref>PMID:19667075</ref> <ref>PMID:19136461</ref> <ref>PMID:19071173</ref> <ref>PMID:20360007</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Transcription preinitiation complexes (PICs) are vital assemblies whose function underlies the expression of protein-encoding genes. Cryo-EM advances have begun to uncover their structural organization. Nevertheless, functional analyses are hindered by incompletely modeled regions. Here we integrate all available cryo-EM data to build a practically complete human PIC structural model. This enables simulations that reveal the assembly's global motions, define PIC partitioning into dynamic communities and delineate how structural modules function together to remodel DNA. We identify key TFIIE-p62 interactions that link core-PIC to TFIIH. p62 rigging interlaces p34, p44 and XPD while capping the DNA-binding and ATP-binding sites of XPD. PIC kinks and locks substrate DNA, creating negative supercoiling within the Pol II cleft to facilitate promoter opening. Mapping disease mutations associated with xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome onto defined communities reveals clustering into three mechanistic classes that affect TFIIH helicase functions, protein interactions and interface dynamics.
+Transcription preinitiation complex structure and dynamics provide insight into genetic diseases.,Yan C, Dodd T, He Y, Tainer JA, Tsutakawa SE, Ivanov I Nat Struct Mol Biol. 2019 May 20. pii: 10.1038/s41594-019-0220-3. doi:, 10.1038/s41594-019-0220-3. PMID:31110295<ref>PMID:31110295</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 6o9l" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 24: / Line 33: @@
 [[Category: Homo sapiens]]
 [[Category: Large Structures]]
+[[Category: Synthetic construct]]
 [[Category: Dodd T]]
 [[Category: He Y]]