View source for 9ehz


==Cryo-EM structure of Human RNA polymerase II Elongation Complex in an Intermediate Translocation State==
<StructureSection load='9ehz' size='340' side='right'caption='[[9ehz]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9ehz]] 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=9EHZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9EHZ 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]] 2.6&#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=9ehz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9ehz OCA], [https://pdbe.org/9ehz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9ehz RCSB], [https://www.ebi.ac.uk/pdbsum/9ehz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9ehz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RPB4_HUMAN RPB4_HUMAN] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. 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. RPB4 is part of a subcomplex with RPB7 that binds to a pocket formed by RPB1, RPB2 and RPB6 at the base of the clamp element. The RBP4-RPB7 subcomplex seems to lock the clamp via RPB7 in the closed conformation thus preventing double-stranded DNA to enter the active site cleft. The RPB4-RPB7 subcomplex binds single-stranded DNA and RNA (By similarity).<ref>PMID:9852112</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Transcription and its regulation pose a major challenge for genome stability. The helicase RECQL5 has been proposed as an important factor to help safeguard the genome, and is the only member of the human RecQ helicase family that directly binds to RNA Polymerase II (Pol II) and affects its progression. RECQL5 mitigates transcription stress and genome instability in cells, yet the molecular mechanism underlying this phenomenon is unclear. Here, we employ cryo-electron microscopy (cryo-EM) to determine the structures of stalled Pol II elongation complexes (ECs) bound to RECQL5. Our structures reveal the molecular interactions stabilizing RECQL5 binding to the Pol II EC and highlight its role as a transcriptional roadblock. Additionally, we find that RECQL5 can modulate the Pol II translocation state. In its nucleotide-free state, RECQL5 mechanically twists the downstream DNA in the EC, and upon nucleotide binding, it undergoes a conformational change that allosterically induces Pol II towards a post-translocation state. We propose this mechanism may help restart Pol II elongation and therefore contribute to reduction of transcription stress.

Structural insights into transcriptional regulation by the helicase RECQL5.,Ariza AJF, Lue NZ, Grob P, Kaeser B, Fang J, Kassube SA, Nogales E bioRxiv [Preprint]. 2025 Jan 29:2025.01.29.634372. doi: , 10.1101/2025.01.29.634372. PMID:39975028<ref>PMID:39975028</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 9ehz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Florez Ariza A]]
[[Category: Lue N]]
[[Category: Nogales E]]