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| | <SX load='6ro4' size='340' side='right' viewer='molstar' caption='[[6ro4]], [[Resolution|resolution]] 3.50Å' scene=''> | | <SX load='6ro4' size='340' side='right' viewer='molstar' caption='[[6ro4]], [[Resolution|resolution]] 3.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6ro4]] is a 9 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RO4 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6RO4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ro4]] is a 9 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=6RO4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RO4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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]] 3.5Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ERCC3, XPB, XPBC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), GTF2H5, C6orf175, TTDA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), ERCC2, XPD, XPDC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), GTF2H3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), GTF2H2, BTF2P44 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), GTF2H4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), XPA, XPAC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_helicase DNA helicase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.4.12 3.6.4.12] </span></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=6ro4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ro4 OCA], [https://pdbe.org/6ro4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ro4 RCSB], [https://www.ebi.ac.uk/pdbsum/6ro4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ro4 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6ro4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ro4 OCA], [http://pdbe.org/6ro4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ro4 RCSB], [http://www.ebi.ac.uk/pdbsum/6ro4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ro4 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://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:[http://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:[http://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> [[http://www.uniprot.org/uniprot/XPA_HUMAN XPA_HUMAN]] Defects in XPA are a cause of xeroderma pigmentosum complementation group A (XP-A) [MIM:[http://omim.org/entry/278700 278700]]; also known as xeroderma pigmentosum type 1 (XP1). XP-A is a rare human autosomal recessive disease characterized by solar sensitivity, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. Group A patients show the most severe skin symptoms and progressive neurological disorders.<ref>PMID:1339397</ref> <ref>PMID:1372103</ref> <ref>PMID:9671271</ref> [[http://www.uniprot.org/uniprot/TF2H5_HUMAN TF2H5_HUMAN]] Defects in GTF2H5 are a cause of trichothiodystrophy photosensitive (TTDP) [MIM:[http://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. [[http://www.uniprot.org/uniprot/ERCC2_HUMAN ERCC2_HUMAN]] Trichothiodystrophy;COFS syndrome;Xeroderma pigmentosum complementation group D. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. | + | [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 == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TF2H3_HUMAN TF2H3_HUMAN]] 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. Anchors XPB. [[http://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> [[http://www.uniprot.org/uniprot/TF2H2_HUMAN TF2H2_HUMAN]] 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. The N-terminus interacts with and regulates XPD whereas an intact C-terminus is required for a successful escape of RNAP II form the promoter. [[http://www.uniprot.org/uniprot/XPA_HUMAN XPA_HUMAN]] Involved in DNA excision repair. Initiates repair by binding to damaged sites with various affinities, depending on the photoproduct and the transcriptional state of the region. Required for UV-induced CHEK1 phosphorylation and the recruitment of CEP164 to cyclobutane pyrimidine dimmers (CPD), sites of DNA damage after UV irradiation.<ref>PMID:19197159</ref> [[http://www.uniprot.org/uniprot/TF2H4_HUMAN TF2H4_HUMAN]] 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. [[http://www.uniprot.org/uniprot/TF2H5_HUMAN TF2H5_HUMAN]] Component of the TFIIH basal transcription factor involved in nucleotide excision repair (NER) of DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. Necessary for the stability of the TFIIH complex and for the presence of normal levels of TFIIH in the cell.<ref>PMID:15220921</ref> [[http://www.uniprot.org/uniprot/ERCC2_HUMAN ERCC2_HUMAN]] ATP-dependent 5'-3' DNA helicase, component of the core-TFIIH basal transcription factor. Involved in nucleotide excision repair (NER) of DNA by opening DNA around the damage, and in RNA transcription by RNA polymerase II by anchoring the CDK-activating kinase (CAK) complex, composed of CDK7, cyclin H and MAT1, to the core-TFIIH complex. Involved in the regulation of vitamin-D receptor activity. As part of the mitotic spindle-associated MMXD complex it plays a role in chromosome segregation. Might have a role in aging process and could play a causative role in the generation of skin cancers.<ref>PMID:10024882</ref> <ref>PMID:15494306</ref> <ref>PMID:20797633</ref> <ref>PMID:8413672</ref> | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: DNA helicase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chernev, A]] | + | [[Category: Chernev A]] |
| - | [[Category: Cramer, P]] | + | [[Category: Cramer P]] |
| - | [[Category: Dienemann, C]] | + | [[Category: Dienemann C]] |
| - | [[Category: Kokic, G]] | + | [[Category: Kokic G]] |
| - | [[Category: Tegunov, D]] | + | [[Category: Tegunov D]] |
| - | [[Category: Urlaub, H]] | + | [[Category: Urlaub H]] |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Dna repair]]
| + | |
| - | [[Category: Helicase]]
| + | |
| - | [[Category: Translocase]]
| + | |
| Structural highlights
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
Nucleotide excision repair (NER) is the major DNA repair pathway that removes UV-induced and bulky DNA lesions. There is currently no structure of NER intermediates, which form around the large multisubunit transcription factor IIH (TFIIH). Here we report the cryo-EM structure of an NER intermediate containing TFIIH and the NER factor XPA. Compared to its transcription conformation, the TFIIH structure is rearranged such that its ATPase subunits XPB and XPD bind double- and single-stranded DNA, consistent with their translocase and helicase activities, respectively. XPA releases the inhibitory kinase module of TFIIH, displaces a 'plug' element from the DNA-binding pore in XPD, and together with the NER factor XPG stimulates XPD activity. Our results explain how TFIIH is switched from a transcription to a repair factor, and provide the basis for a mechanistic analysis of the NER pathway.
Structural basis of TFIIH activation for nucleotide excision repair.,Kokic G, Chernev A, Tegunov D, Dienemann C, Urlaub H, Cramer P Nat Commun. 2019 Jun 28;10(1):2885. doi: 10.1038/s41467-019-10745-5. PMID:31253769[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
- ↑ Kokic G, Chernev A, Tegunov D, Dienemann C, Urlaub H, Cramer P. Structural basis of TFIIH activation for nucleotide excision repair. Nat Commun. 2019 Jun 28;10(1):2885. doi: 10.1038/s41467-019-10745-5. PMID:31253769 doi:http://dx.doi.org/10.1038/s41467-019-10745-5
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