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6nmi
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 6nmi is ON HOLD Authors: Description: Category: Unreleased Structures) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Cryo-EM structure of the human TFIIH core complex== | |
| + | <SX load='6nmi' size='340' side='right' viewer='molstar' caption='[[6nmi]], [[Resolution|resolution]] 3.70Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6nmi]] is a 8 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=6NMI OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6NMI 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> | ||
| + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</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'>[http://proteopedia.org/fgij/fg.htm?mol=6nmi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nmi OCA], [http://pdbe.org/6nmi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nmi RCSB], [http://www.ebi.ac.uk/pdbsum/6nmi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nmi ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == 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. | ||
| + | == 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/MAT1_HUMAN MAT1_HUMAN]] Stabilizes the cyclin H-CDK7 complex to form a functional CDK-activating kinase (CAK) enzymatic complex. CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the repetitive C-terminus domain (CTD) of its large subunit (POLR2A), allowing its escape from the promoter and elongation of the transcripts. Involved in cell cycle control and in RNA transcription by RNA polymerase II.<ref>PMID:10024882</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. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Transcription factor IIH (TFIIH) is a heterodecameric protein complex critical for transcription initiation by RNA polymerase II and nucleotide excision DNA repair. The TFIIH core complex is sufficient for its repair functions and harbors the XPB and XPD DNA-dependent ATPase/helicase subunits, which are affected by human disease mutations. Transcription initiation additionally requires the CdK activating kinase subcomplex. Previous structural work has provided only partial insight into the architecture of TFIIH and its interactions within transcription pre-initiation complexes. Here, we present the complete structure of the human TFIIH core complex, determined by phase-plate cryo-electron microscopy at 3.7 A resolution. The structure uncovers the molecular basis of TFIIH assembly, revealing how the recruitment of XPB by p52 depends on a pseudo-symmetric dimer of homologous domains in these two proteins. The structure also suggests a function for p62 in the regulation of XPD, and allows the mapping of previously unresolved human disease mutations. | ||
| - | + | The complete structure of the human TFIIH core complex.,Greber BJ, Toso DB, Fang J, Nogales E Elife. 2019 Mar 12;8. pii: 44771. doi: 10.7554/eLife.44771. PMID:30860024<ref>PMID:30860024</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6nmi" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </SX> | ||
| + | [[Category: DNA helicase]] | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Fang, J]] | ||
| + | [[Category: Greber, B J]] | ||
| + | [[Category: Nogales, E]] | ||
| + | [[Category: Toso, D]] | ||
| + | [[Category: Dna repair]] | ||
| + | [[Category: Helicase]] | ||
| + | [[Category: Multiprotein complex]] | ||
| + | [[Category: Transcription]] | ||
Current revision
Cryo-EM structure of the human TFIIH core complex
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