8p4c: Difference between revisions

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'''Unreleased structure'''


The entry 8p4c is ON HOLD  until sometime in the future
==Structural insights into human co-transcriptional capping - structure 3==
<StructureSection load='8p4c' size='340' side='right'caption='[[8p4c]], [[Resolution|resolution]] 3.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8p4c]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] 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=8P4C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8P4C 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]] 3.8&#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=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=8p4c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8p4c OCA], [https://pdbe.org/8p4c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8p4c RCSB], [https://www.ebi.ac.uk/pdbsum/8p4c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8p4c ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RPB1_CRIGR RPB1_CRIGR] 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 (By similarity). Regulation of gene expression levels depends on the balance between methylation and acetylation levels of tha CTD-lysines (By similarity). Initiation or early elongation steps of transcription of growth-factors-induced immediate early genes are regulated by the acetylation status of the CTD (By similarity). Methylation and dimethylation have a repressive effect on target genes expression (By similarity).[UniProtKB:P08775][UniProtKB:P24928]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Co-transcriptional capping of the nascent pre-mRNA 5' end prevents degradation of RNA polymerase (Pol) II transcripts and suppresses the innate immune response. Here, we provide mechanistic insights into the three major steps of human co-transcriptional pre-mRNA capping based on six different cryoelectron microscopy (cryo-EM) structures. The human mRNA capping enzyme, RNGTT, first docks to the Pol II stalk to position its triphosphatase domain near the RNA exit site. The capping enzyme then moves onto the Pol II surface, and its guanylyltransferase receives the pre-mRNA 5'-diphosphate end. Addition of a GMP moiety can occur when the RNA is approximately 22 nt long, sufficient to reach the active site of the guanylyltransferase. For subsequent cap(1) methylation, the methyltransferase CMTR1 binds the Pol II stalk and can receive RNA after it is grown to approximately 29 nt in length. The observed rearrangements of capping factors on the Pol II surface may be triggered by the completion of catalytic reaction steps and are accommodated by domain movements in the elongation factor DRB sensitivity-inducing factor (DSIF).


Authors:  
Structural insights into human co-transcriptional capping.,Garg G, Dienemann C, Farnung L, Schwarz J, Linden A, Urlaub H, Cramer P Mol Cell. 2023 Jun 21:S1097-2765(23)00424-0. doi: 10.1016/j.molcel.2023.06.002. PMID:37369200<ref>PMID:37369200</ref>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 8p4c" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Sus scrofa]]
[[Category: Synthetic construct]]
[[Category: Cramer P]]
[[Category: Dienemann C]]
[[Category: Farnung L]]
[[Category: Garg G]]
[[Category: Linden A]]
[[Category: Schwarz J]]
[[Category: Urlaub H]]

Latest revision as of 11:29, 16 August 2023

Structural insights into human co-transcriptional capping - structure 3Structural insights into human co-transcriptional capping - structure 3

Structural highlights

8p4c is a 10 chain structure with sequence from Homo sapiens, Sus scrofa and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 3.8Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RPB1_CRIGR 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 (By similarity). Regulation of gene expression levels depends on the balance between methylation and acetylation levels of tha CTD-lysines (By similarity). Initiation or early elongation steps of transcription of growth-factors-induced immediate early genes are regulated by the acetylation status of the CTD (By similarity). Methylation and dimethylation have a repressive effect on target genes expression (By similarity).[UniProtKB:P08775][UniProtKB:P24928]

Publication Abstract from PubMed

Co-transcriptional capping of the nascent pre-mRNA 5' end prevents degradation of RNA polymerase (Pol) II transcripts and suppresses the innate immune response. Here, we provide mechanistic insights into the three major steps of human co-transcriptional pre-mRNA capping based on six different cryoelectron microscopy (cryo-EM) structures. The human mRNA capping enzyme, RNGTT, first docks to the Pol II stalk to position its triphosphatase domain near the RNA exit site. The capping enzyme then moves onto the Pol II surface, and its guanylyltransferase receives the pre-mRNA 5'-diphosphate end. Addition of a GMP moiety can occur when the RNA is approximately 22 nt long, sufficient to reach the active site of the guanylyltransferase. For subsequent cap(1) methylation, the methyltransferase CMTR1 binds the Pol II stalk and can receive RNA after it is grown to approximately 29 nt in length. The observed rearrangements of capping factors on the Pol II surface may be triggered by the completion of catalytic reaction steps and are accommodated by domain movements in the elongation factor DRB sensitivity-inducing factor (DSIF).

Structural insights into human co-transcriptional capping.,Garg G, Dienemann C, Farnung L, Schwarz J, Linden A, Urlaub H, Cramer P Mol Cell. 2023 Jun 21:S1097-2765(23)00424-0. doi: 10.1016/j.molcel.2023.06.002. PMID:37369200[1]

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

References

  1. Garg G, Dienemann C, Farnung L, Schwarz J, Linden A, Urlaub H, Cramer P. Structural insights into human co-transcriptional capping. Mol Cell. 2023 Jun 21:S1097-2765(23)00424-0. PMID:37369200 doi:10.1016/j.molcel.2023.06.002

8p4c, resolution 3.80Å

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