4ern: Difference between revisions

Latest revision as of 15:08, 14 March 2024

Crystal structure of the C-terminal domain of human XPB/ERCC-3 excision repair protein at 1.80 A

Structural highlights

4ern is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.8Å
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]

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

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OCA

[1] 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

[2] 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

[3] 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

[4] 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

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[2]

[3]

[4]

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4ern]] is a 1 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=4ERN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ERN FirstGlance]. <br>
-</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=4ern FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ern OCA], [https://pdbe.org/4ern PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ern RCSB], [https://www.ebi.ac.uk/pdbsum/4ern PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ern ProSAT]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</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=4ern FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ern OCA], [https://pdbe.org/4ern PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ern RCSB], [https://www.ebi.ac.uk/pdbsum/4ern PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ern ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 10: / Line 11: @@
 == 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 ==
-XPB is a DNA-dependent helicase and a subunit of the TFIIH complex required for both transcription and DNA repair. XPB contains four domains: an N-terminal domain, two conserved helicase domains (HD1 and HD2) and a C-terminal extension. The C-terminal extension is important for DNA repair since the phosphorylation of Ser751 inhibits 5'-incision by ERCC1-XPF endonuclease. A disease-causing frameshift mutation (XP11BE) that changes the last 42 amino acids of XPB causes manifestations including impaired DNA repair and deficient transcription. Here, the crystal structure of the C-terminal half of XPB (residues 494-782) is reported at 1.8 A resolution. The structure contained the conserved XPB HD2 and a C-terminal extension which shares structural similarity with RIG-I, leading to a structural model of the XPF-XPB-DNA complex for 5' incision during DNA repair. A mutation mimicking the XP11BE mutation produced the much less soluble mutant XPBm(494-781). Western blotting results confirmed that the intracellular levels of XPB and other TFIIH subunits in XP11BE patient cells were much lower than those from the healthy parents. Together, these results indicate that the XP11BE mutation not only divests the XPF-interaction motif, impairing DNA repair, but also reduces XPB solubility, leading to a lower intracellular level of TFIIH and deficient transcription.
-Structure of the C-terminal half of human XPB helicase and the impact of the disease-causing mutation XP11BE.,Hilario E, Li Y, Nobumori Y, Liu X, Fan L Acta Crystallogr D Biol Crystallogr. 2013 Feb;69(Pt 2):237-46. doi:, 10.1107/S0907444912045040. Epub 2013 Jan 19. PMID:23385459<ref>PMID:23385459</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 4ern" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4ern: Difference between revisions

Latest revision as of 15:08, 14 March 2024

Crystal structure of the C-terminal domain of human XPB/ERCC-3 excision repair protein at 1.80 A

Structural highlights

Disease

Function

References

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