8byq

From Proteopedia

(Difference between revisions)

Current revision

RNA polymerase II pre-initiation complex with the proximal +1 nucleosome (PIC-Nuc10W)

Structural highlights

8byq is a 10 chain structure with sequence from Homo sapiens and Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 4.1Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

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: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.^[1] ^[2] Defects in ERCC3 are a cause of trichothiodystrophy photosensitive (TTDP) [MIM: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.^[3]

Function

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.^[4]

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^[5]

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

References

↑ Vermeulen W, Scott RJ, Rodgers S, Muller HJ, Cole J, Arlett CF, Kleijer WJ, Bootsma D, Hoeijmakers JH, Weeda G. Clinical heterogeneity within xeroderma pigmentosum associated with mutations in the DNA repair and transcription gene ERCC3. Am J Hum Genet. 1994 Feb;54(2):191-200. PMID:8304337
↑ Oh KS, Khan SG, Jaspers NG, Raams A, Ueda T, Lehmann A, Friedmann PS, Emmert S, Gratchev A, Lachlan K, Lucassan A, Baker CC, Kraemer KH. Phenotypic heterogeneity in the XPB DNA helicase gene (ERCC3): xeroderma pigmentosum without and with Cockayne syndrome. Hum Mutat. 2006 Nov;27(11):1092-103. PMID:16947863 doi:10.1002/humu.20392
↑ Weeda G, Eveno E, Donker I, Vermeulen W, Chevallier-Lagente O, Taieb A, Stary A, Hoeijmakers JH, Mezzina M, Sarasin A. A mutation in the XPB/ERCC3 DNA repair transcription gene, associated with trichothiodystrophy. Am J Hum Genet. 1997 Feb;60(2):320-9. PMID:9012405
↑ Tirode F, Busso D, Coin F, Egly JM. Reconstitution of the transcription factor TFIIH: assignment of functions for the three enzymatic subunits, XPB, XPD, and cdk7. Mol Cell. 1999 Jan;3(1):87-95. PMID:10024882
↑ Abril-Garrido J, Dienemann C, Grabbe F, Velychko T, Lidschreiber M, Wang H, Cramer P. Structural basis of transcription reduction by a promoter-proximal +1 nucleosome. Mol Cell. 2023 Jun 1;83(11):1798-1809.e7. PMID:37148879 doi:10.1016/j.molcel.2023.04.011

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8byq"

@@ Line 3: / Line 3: @@
 <StructureSection load='8byq' size='340' side='right'caption='[[8byq]], [[Resolution|resolution]] 4.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[8byq]] 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/Unidentified_adenovirus Unidentified adenovirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8BYQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BYQ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[8byq]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8BYQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BYQ FirstGlance]. <br>
-</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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.1&#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=8byq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8byq OCA], [https://pdbe.org/8byq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8byq RCSB], [https://www.ebi.ac.uk/pdbsum/8byq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8byq ProSAT]</span></td></tr>
 </table>
@@ Line 11: / Line 12: @@
 == 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 8byq" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[RNA polymerase 3D structures|RNA polymerase 3D structures]]
 == References ==
 <references/>
@@ Line 18: / Line 31: @@
 [[Category: Large Structures]]
 [[Category: Sus scrofa]]
-[[Category: Unidentified adenovirus]]
 [[Category: Abril-Garrido J]]
 [[Category: Cramer P]]

8byq

From Proteopedia

Current revision

RNA polymerase II pre-initiation complex with the proximal +1 nucleosome (PIC-Nuc10W)

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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