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| ==Human core TFIIH bound to DNA within the PIC== | | ==Human core TFIIH bound to DNA within the PIC== |
| <StructureSection load='5ivw' size='340' side='right' caption='[[5ivw]], [[Resolution|resolution]] 10.00Å' scene=''> | | <SX load='5ivw' size='340' side='right' viewer='molstar' caption='[[5ivw]], [[Resolution|resolution]] 10.00Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[5ivw]] is a 7 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IVW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5IVW FirstGlance]. <br> | | <table><tr><td colspan='2'>[[5ivw]] is a 8 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=5IVW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IVW FirstGlance]. <br> |
| </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5iy6|5iy6]], [[5iya|5iya]], [[5iy7|5iy7]], [[5iy8|5iy8]], [[5iy9|5iy9]], [[5iyb|5iyb]], [[5iyc|5iyc]], [[5iyd|5iyd]]</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]] 10Å</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=5ivw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ivw OCA], [https://pdbe.org/5ivw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ivw RCSB], [https://www.ebi.ac.uk/pdbsum/5ivw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ivw ProSAT]</span></td></tr> |
| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ivw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ivw OCA], [http://pdbe.org/5ivw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ivw RCSB], [http://www.ebi.ac.uk/pdbsum/5ivw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ivw ProSAT]</span></td></tr> | |
| </table> | | </table> |
| == Disease == | | == Disease == |
| [[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/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/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/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. |
| == 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/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/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/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> [[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. | | [https://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> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| In eukaryotic transcription initiation, a large multi-subunit pre-initiation complex (PIC) that assembles at the core promoter is required for the opening of the duplex DNA and identification of the start site for transcription by RNA polymerase II. Here we use cryo-electron microscropy (cryo-EM) to determine near-atomic resolution structures of the human PIC in a closed state (engaged with duplex DNA), an open state (engaged with a transcription bubble), and an initially transcribing complex (containing six base pairs of DNA-RNA hybrid). Our studies provide structures for previously uncharacterized components of the PIC, such as TFIIE and TFIIH, and segments of TFIIA, TFIIB and TFIIF. Comparison of the different structures reveals the sequential conformational changes that accompany the transition from each state to the next throughout the transcription initiation process. This analysis illustrates the key role of TFIIB in transcription bubble stabilization and provides strong structural support for a translocase activity of XPB.
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| Near-atomic resolution visualization of human transcription promoter opening.,He Y, Yan C, Fang J, Inouye C, Tjian R, Ivanov I, Nogales E Nature. 2016 May 11;533(7603):359-65. doi: 10.1038/nature17970. PMID:27193682<ref>PMID:27193682</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 5ivw" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
| *[[Helicase|Helicase]] | | *[[Helicase 3D structures|Helicase 3D structures]] |
| | *[[Transcription initiation factors 3D structures|Transcription initiation factors 3D structures]] |
| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </SX> |
| [[Category: DNA helicase]]
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| [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| [[Category: Fang, J]] | | [[Category: Large Structures]] |
| [[Category: He, Y]] | | [[Category: Fang J]] |
| [[Category: Inouye, C]] | | [[Category: He Y]] |
| [[Category: Ivanov, I]] | | [[Category: Inouye C]] |
| [[Category: Nogales, E]] | | [[Category: Ivanov I]] |
| [[Category: Tjian, R]] | | [[Category: Nogales E]] |
| [[Category: Yan, C]] | | [[Category: Tjian R]] |
| [[Category: Human]]
| | [[Category: Yan C]] |
| [[Category: Initiation]]
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| [[Category: Rna polymerase ii]]
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| [[Category: Transcription-dna complex]]
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