View source for 8bvw


==RNA polymerase II pre-initiation complex with the distal +1 nucleosome (PIC-Nuc18W)==
<StructureSection load='8bvw' size='340' side='right'caption='[[8bvw]], [[Resolution|resolution]] 4.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8bvw]] 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=8BVW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BVW 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]] 4&#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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8bvw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bvw OCA], [https://pdbe.org/8bvw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bvw RCSB], [https://www.ebi.ac.uk/pdbsum/8bvw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bvw ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/ERCC3_HUMAN ERCC3_HUMAN] IBIDS syndrome;Xeroderma pigmentosum complementation group B;PIBIDS syndrome;Xeroderma pigmentosum/Cockayne syndrome complex. Defects in ERCC3 are the cause of xeroderma pigmentosum complementation group B (XP-B) [MIM:[https://omim.org/entry/610651 610651]; also known as xeroderma pigmentosum II (XP2) or XP group B (XPB) or xeroderma pigmentosum group B combined with Cockayne syndrome (XP-B/CS). Xeroderma pigmentosum is an autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. Some XP-B patients present features of Cockayne syndrome, including dwarfism, sensorineural deafness, microcephaly, mental retardation, pigmentary retinopathy, ataxia, decreased nerve conduction velocities.<ref>PMID:8304337</ref> <ref>PMID:16947863</ref>   Defects in ERCC3 are a cause of trichothiodystrophy photosensitive (TTDP) [MIM:[https://omim.org/entry/601675 601675]. TTDP is an autosomal recessive disease characterized by sulfur-deficient brittle hair and nails, ichthyosis, mental retardation, impaired sexual development, abnormal facies and cutaneous photosensitivity correlated with a nucleotide excision repair (NER) defect. Neonates with trichothiodystrophy and ichthyosis are usually born with a collodion membrane. The severity of the ichthyosis after the membrane is shed is variable, ranging from a mild to severe lamellar ichthyotic phenotype. There are no reports of skin cancer associated with TTDP.<ref>PMID:9012405</ref> 
== Function ==
[https://www.uniprot.org/uniprot/ERCC3_HUMAN ERCC3_HUMAN] ATP-dependent 3'-5' DNA helicase, component of the core-TFIIH basal transcription factor, involved in nucleotide excision repair (NER) of DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. Acts by opening DNA either around the RNA transcription start site or the DNA damage.<ref>PMID:10024882</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
At active human genes, the +1 nucleosome is located downstream of the RNA polymerase II (RNA Pol II) pre-initiation complex (PIC). However, at inactive genes, the +1 nucleosome is found further upstream, at a promoter-proximal location. Here, we establish a model system to show that a promoter-proximal +1 nucleosome can reduce RNA synthesis in vivo and in vitro, and we analyze its structural basis. We find that the PIC assembles normally when the edge of the +1 nucleosome is located 18 base pairs (bp) downstream of the transcription start site (TSS). However, when the nucleosome edge is located further upstream, only 10 bp downstream of the TSS, the PIC adopts an inhibited state. The transcription factor IIH (TFIIH) shows a closed conformation and its subunit XPB contacts DNA with only one of its two ATPase lobes, inconsistent with DNA opening. These results provide a mechanism for nucleosome-dependent regulation of transcription initiation.

Structural basis of transcription reduction by a promoter-proximal +1 nucleosome.,Abril-Garrido J, Dienemann C, Grabbe F, Velychko T, Lidschreiber M, Wang H, Cramer P Mol Cell. 2023 Jun 1;83(11):1798-1809.e7. doi: 10.1016/j.molcel.2023.04.011. Epub , 2023 May 5. PMID:37148879<ref>PMID:37148879</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8bvw" style="background-color:#fffaf0;"></div>

==See Also==
*[[RNA polymerase 3D structures|RNA polymerase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Abril-Garrido J]]
[[Category: Cramer P]]
[[Category: Dienemann C]]
[[Category: Grabbe F]]
[[Category: Lidschreiber M]]
[[Category: Velychko T]]
[[Category: Wang H]]